Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation... Background: To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Methods: Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). Results: The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease- free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. Conclusion: HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long- term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted. Page 1 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 Background Methods Cervical cancer is the second most frequent cancer among Patient's characteristics Between November 1st, 2006 to May 31, 2009, 10 women worldwide [1]. It has demonstrated the superior- ity of combined chemotherapy with radiotherapy (RT) in patients undergoing whole pelvic HT (WPHT) for locally the treatment of advanced cervix cancer [2,3]. The radia- advanced cervical cancer without pelvic or paraarotic lym- tion therapy consists of external beam irradiation to the phadenopathy at Far Eastern Memorial Hospital (FEMH) primary tumor and corresponding region of lymphatic were retrospectively enrolled. Staging investigations drainage, followed by brachytherapy to boost the gross included complete history and physical examination, tumor in the cervix. A significant benefit of chemoradia- fiberoptic endoscopic evaluation, complete blood counts, tion on both overall survival and progress-free survival liver and renal function tests, chest X-ray, magnetic reso- rate was mentioned [4]. However, grade 3 or 4 haemato- nance imaging (MRI) scans or computed tomography logical (white cell count, 16% vs. 8%; platelets, 1·5% vs. (CT) scans of the pelvic region. The disease was staged 0·2%; haematological not otherwise specified, 29% vs. according to the International Federation of Gynecology 1%) and gastrointestinal toxicities (9% vs. 4%) signifi- and Obstetrics (FIGO) criteria [15]. cantly greater in the concomitant chemoradiation group than the RT alone group should also be mentioned. Tan et Radiotherapy al. [5] also proposed a late toxicity observation for con- Radiotherapy was administered to the whole pelvic region comitant chemoradiation of locally advanced cervical in 28 fractions totaling 50.4 Gy followed by intracavitary cancer. There were 14.5%, 9.4% and 11.4% for grade 3 or brachytherapy. The total dose of brachytherapy delivered 4 urinary, bowel and affecting other organs complica- was 30 Gy/6 fractions in patients. The total dose delivered tions, respectively. to point A (a reference location 2 cm lateral and 2 cm superior to the cervical os) was 80.4 Gy in patients; the With the advances in radiotherapy modalities, whole pel- total dose delivered to point p (the pelvic wall) was 55.0 vic intensity-modulated radiotherapy (WP-IMRT) applied Gy in patients. Cisplatin (CDDP) was administered dur- to gynecologic malignancies with excellent planning tar- ing external radiation, beginning on the first day of radia- get volume (PTV) coverage and is associated with less tion for 5 weeks concurrent with WPHT. A dose of 40 mg/ CDDP (maximum dose, 70 mg) was used and admin- acute gastrointestinal sequelae than conventional whole m pelvic radiotherapy (WPRT) as reported by Mundt et al. istered via a peripheral vein to patients. [6]. Under similar target coverage, IMRT is superior to conventional techniques in normal tissue sparing for the Immobilization treatment of cervical cancer and a number of groups have A BlueBAG™ immobilization system (Medical Intelli- explored IMRT in the gynecologic setting as a method to gence, Schwabmünchen, Germany) was used for each of minimize the gastrointestinal, genitourinary, and bone these patients to fix pelvic and extremities. Positioning marrow toxicity that occurs in conventional RT [7-11]. was supine with arms up, and feet placed in an ankle holder. All patients underwent a CT planning scan with Helical tomotherapy (HT) is a new CT-based rotational our departmental scanner (Siemens Somatom Plus 4 CT intensity modulated radiotherapy and provides an scanner) from the diaphragm to 5 cm below the ischial impressive ability for highly conformal dose distributions tuberosities. Localization marks were placed on anterior and simultaneous critical organ sparing ability [12,13]. and lateral sides of the patients at the mid-plane and mid- HT is being tested to apply for gynecologic malignancies line at the level of L4-L5 vertebral body interspace. CT recently and provides encouraging results about excellent with 5-mm slice thickness was taken for treatment plan- setup accuracy and reducing margins for the external ning. Target objects and normal structures were contoured beam treatment of gynecologic malignancies [14]. How- on a Pinnacle3 treatment planning system (Philips ever, this report did not provide the clinical results about Healthcare, Madison, Wisconsin, USA). The MRI or CT the gynecologic malignancies treated by HT. images were retrieved on a Pinnacle workstation and fused with the CT images for contouring of the tumor vol- In our institute, a Tomotherapy Hi-Art system (Tomother- ume. apy, Inc., Madison, Wisconsin, USA) was installed and used for treatment from November 2006. We report here Delineation of target volumes our initial clinical 2 years experience for patients with Delineation and constraints was according to Radiation locally advanced cervical cancer with HT, focusing on the Therapy Oncology Group (RTOG) 0418 protocol and the correlation between dosimetry, clinical outcome and early International Commission on Radiation Units and Meas- toxicities. urements reports 50 [16] and 62 [17] recommendations. The Gross Tumor Volume (GTV) was defined as all known Page 2 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 gross disease determined from CT, clinical information, as follows: small bowel (2 cm above the most superior and MRI. The Clinical Target Volume (CTV) was defined vessel contour) < 30% to receive ≥ 40 Gy, minor deviation as areas considered containing potential microscopic dis- 30% to 40 Gy; Rectum < 60% to receive ≥ 30 Gy, minor ease. Internal Target Volume (ITV) was defined as the vol- deviation 35% to 50 Gy; Bladder < 35% to receive ≥ 45 ume of the vagina and paravaginal soft tissues that is in Gy, minor deviation 35% to 50 Gy; Femoral head ≤ 15% both the empty and full bladder CT scans that were done to receive ≥ 30 Gy, minor deviation 20% to 30 Gy. at the time of simulation and fused together. The Planning Target Volume (PTV) would provide a 7 mm margin Intracavitary brachytherapy (anteriorly, posteriorly, laterally, as well as in the superior An iridium-192 (high-dose-rate) source was used with and inferior directions) around the nodal CTV and ITV. standard Fletcher-Suit-Delclos intracavitary applicators. The treatment plan would be done on the full bladder Patients were treated twice a week after WPHT completed scan. The treatment plan used for each patient would be for 3 weeks, with a prescribed dose of 500 cGy per fraction based on an analysis of the volumetric dose, including to Point A. The high-dose rate (HDR) source dwell times dose volume histogram (DVH) analyses of the PTV and were manually calculated based on our institutional sys- critical normal structures. The GTV plus a 7-mm expan- tem of empiric intracavitary irradiation rules. Postimplan- sion was defined as the primary tumor CTV to account for tation dosimetry was performed with the GENIE microscopic spread, excluding the bowel, bladder, and treatment planning system v1.0.4 (Nucletron, Nether- rectum if they were not clinically involved); The nodal land), and included calculation of dose to the "classical" CTV should include the internal (hypogastric and obtura- Point A bilaterally (a reference location 2 cm lateral and 2 tor), external, common iliac lymph nodes perinodal tis- cm superior to the cervical os), pelvic sidewall bilaterally sue, pertinent clips and down to the level of S3. (Point P, defined as the point 2 cm above the top of the Identification of the CTV usually began with the identifi- colpostat and 6 cm lateral to midline), and the rectal cation of the iliac vessels. The average margin would be 7 point and bladder point as defined by the International mm. Bone and intraperitoneal small bowel should be Commission on Radiation Units and Measurements [19]. excluded from the CTV; also, iliopsoas muscle that lies For each implant, point doses to Points A and P, the blad- adjacent to clinically negative lymph nodes should also be der point, and the rectal point were recorded; after com- excluded from the CTV. Approximately 1.5 cm of tissue pletion of therapy, the doses for the six implants were anterior to the S1, S2 and S3 sacral segments was usually summed. There is no standard or universally accepted added to the CTV in order to include the presacral lymph fraction size for HDR brachytherapy. At our institution we nodes and uterosacral ligaments. The most antero-lateral have chosen to use the fraction size of 500 cGy. external iliac lymph nodes that lied just proximal to the inguinal canal should be excluded from the CTV. The CTV Conventional treatment planning for comparison of the nodes should end 7 mm from L4/L5 interspace to Conventional whole pelvic radiation therapy (WPRT) account for the PTV. The PTV for nodes stopped at L4/L5 plans were generated using Pinnacle3 treatment planning interspace. The vaginal and parametrial CTV should actu- system (Philips Healthcare, Madison, Wisconsin, USA). ally be an ITV, which will account for internal organ The isocenter was placed at the geometric center of the motion. The inferior limit was usually around the level of PTV. A 4-field "box" plan was designed using 6-MV pho- the upper third of the symphysis pubis but could be indi- tons with apertures shaped to the PTV in each beam's eye- vidualized based on inferior spread of the patient's tumor. view. The pelvic field extended from the upper margin of The lateral margin of the vaginal PTV should be to the L5 to the midportion of the obturator foramen or the low- obturator muscle. However, at least 3 cm of the vagina est level of disease, with a 2-cm margin, and laterally 1.5 needed to be treated or at least 1 cm below the obturator cm beyond the lateral margins of the bony pelvic wall (at foramen. The 90% isodose surface covered between 95% least 7 cm from the midline). For the lateral fields, the and 98% of the PTV 50.4, or volumes of overdose exceed anterior border was the pubic symphysis and the posterior 115% < 5% of the PTV 50.4 volume could be considered border was the space between S2 and S3. The fields could acceptable. The field width, pitch, and modulation factor be modified to include areas of known tumor and wedges (MF) usually used for the WPHT treatment planning opti- were used as needed. All plans were normalized to cover mization were 2.5 cm, 0.32 and 3.0, respectively. All 98% of the PTV with 50.4 Gy. The 2% underdose repre- patients received daily megavoltage computed tomogra- sents those voxels at the periphery. This normalization phy (MVCT) acquisitions for setup verification [18]. provided conformal coverage while minimizing dose nonuniformity within the target. Normal structures will be contoured using the full-blad- der CT scan. The OARs (i.e., bladder, rectum, sigmoid, Dose-volume analysis of treatment plans small bowel, and femoral heads) were contoured as solid Dose-volume histograms (DVHs) of the PTVs and the crit- organs. Dose-volume constraints for normal tissues were ical normal structures were analyzed accordingly. For Page 3 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 PTVs, we evaluated the volume, the volume covered by survival was calculated from the date of pathologic proof 95% of the prescription dose (V95), and the minimum to the date of the first physical or radiographic evidence of ) and 95% (D ) of the PTV. The doses delivered to 5% (D disease progression, death, or the last follow-up visit. Sur- 5 95 critical organs with functional subunits organized in a vival was calculated from the date of pathologic proof to series were examined. The conformal index (CI) and the the date of death or the last follow-up visit. All analyses uniformity index (UI) had been used to evaluate the con- were performed using the Statistical Package for the Social formity and uniformity of the plan. The volume received Sciences, version 12.0 (SPSS, Chicago, IL, USA). the mean dose for PTV generated from the DVH. The con- formal index (CI) for PTV was calculated using the for- Results mula CI = V /V , where V was the ratio of the Patient characteristics ICRU TV PTV TV treated volume enclosed by the prescription isodose sur- Ten women were included. They had a median age of 58 face and V was the planning target volume [17]. The years (range, 33-72 years). All belong to FIGO Stage IIB PTV uniformity index (UI) was defined as UI = D /D , where and IIIB. The medium tumor volume was 45.9 cm . The 5 95 D and D were the minimum doses delivered to 5% and medium weekly cycles of chemotherapy were 5 weeks. 5 95 95% of the PTV reported previously [20]. Seventy percent of patients could complete 4 weekly cycles of chemotherapy. All of the patients were treated Toxicity with definitively concurrent chemotherapy with WPHT Interruptions in radiotherapy might be necessitated by followed by brachytherapy. (Table 1) uncontrolled diarrhea, or other acute complications. If radiation therapy was held, then chemotherapy would Treatment outcome also be held. Chemotherapy stopped at the completion of The mean survival was 25 months (range, 3 to 27 RT. If chemotherapy was held, radiation therapy would months). The actuarial 2-year overall survival, progress- continue. Radiation was only stopped in cases of grade 4 free survival, locoregional control and distant metastasis- hematologic or non-hematologic toxicity until toxicity free rates were 67%, 77%, 90% and 88%, respectively. The resolved to at least grade 3. CDDP was withheld in any 2-year survival, progression-free, locoregional-progres- case involving grade 3 toxicity until the toxicity regressed sion-free and distant metastasis-free patient number over to any grade of <3; in patients with grade 3 toxicity that all patients are 9/10, 8/10, 9/10 and 9/10, respectively. persisted >2 weeks, chemotherapy was no longer admin- Ninety percent of patients were surviving at the time of istered. this report. Follow-up Dose-volume analysis and comparison for WPHT and Upon treatment completion, patients were evaluated WPRT every 3 months for the first year, every 4 months during The WPHT for UI and CI was 1.07 ± 0.05 and 1.01 ± 0.05, the second year, every 6 months during the third year, and respectively. The UI and CI for individual patient are plot- annually thereafter. At each visit, a physical and pelvic ted in Figures 1A and 1B, respectively. Dose-volume histo- examination, blood counts, clinical chemistry, and chest grams statistics for the organs at risk are described in table x-rays were performed. Computed tomography (CT) scan, 2. WPHT provided better critical organs sparing than ultrasound (US), and other imaging studies were con- WPRT in the mean dose and the other parameters for rec- ducted when appropriate. Suspected cases of persistent or tum, bladder and intestine with a statistically significant recurrent disease were confirmed by biopsy whenever pos- level (p value < 0.01), respectively. WPHT provided sible. Acute and late toxicities (occurring >90 days after impressive ability of high dose declining for OARs than beginning RT) were defined and graded according to the WPRT. However, WPHT had poorer results for right and Common Terminology Criteria for Adverse Events v3.0 left side pelvic bone sparing than WPRT due to lacking of (CTCAE v3.0). V10 and V20 constraint for planning initially. Statistical methods Acute and subacute toxicity Descriptive statistics (mean, median, proportions) were Acute toxicity of radiation therapy within chemotherapy calculated to characterize the patient, disease, and treat- and late toxicity is detailed in Additional file 1. One grade ment features as well as toxicities after treatment. The 3 of acute toxicity for diarrhea, thrombocytopenia and overall survival (OS), progression-free survival (PFS), three grade 3 of leucopenia were noted during CCRT. locoregional progression-free (LRPF), and distant metas- Only one grade 3 of subacute toxicity for thrombocytope- tases-free (DMF) rates were estimated using the Kaplan- nia was noted. There was no grade 3 or 4 subacute toxici- Meier product-limit method. Progression was defined as a ties for anemia, leucopenia, genitourinary or 50 percent increase in the product of the two largest diam- gastrointestinal. eters of the primary tumor or metastasis. Progression-free Page 4 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 Table 1: Patient characteristics Variable No. of patient (%) Age (years) Median (range) 58 (33-72) Gender Female 10 (100%) Karnofsky performance status < 70 0 ≥ 70 10 (100%) Pathology Squamous cell carcinoma 7 (70%) Adenocarcinoma 3 (30%) International Federation of Gynecology and Obstetrics (FIGO) stage Stage IIB 9 (90%) Stage IIIB 1 (10%) Tumor size Medium length (range) 5.5 cm (4.3 - 8.4 cm) Medium depth (range) 3.7 cm (2.4 - 4.6 cm) Medium width (range) 4.4 cm (3.5 - 6.0 cm) Weekly cycles of chemotherapy 5 weeks 5 (50%) 4 weeks 2 (20%) 3 weeks 1 (10%) 2 weeks 2 (20%) tion of the prescription dose was delivered outside the Discussion In our preliminary results of locally advanced cervical can- PTV. The greater the CI, the less is the dose conformity to cer receiving WPHT concurrent with chemotherapy fol- the PTV [20]. The greater UI indicates higher heterogene- lowed by brachytherapy, HT provides feasible outcomes ity in the PTV [22]. In the current study, the UI and CI for and acceptable toxicity during and after CCRT. WPHT was 1.07 ± 0.05 and 1.01 ± 0.05, respectively. WPHT provides the impressed conformality and uniform- The 2-year estimate of OS, PFS, locoregional failure only ity for locally advanced cervical carcinoma patients. The and distant metastasis only rate in the RT plus weekly UI and CI for individual patient are described in Fig. 1A CDDP reported by randomized trials was 67 - 71%, 64 - and 1B, respectively. 84%, 10 - 25% and 6 - 11%, respectively [2,3,21]. The overall survival, disease-free survival, locoregional failure Despite the clear efficacy of a combined modality and distant metastasis rate at 2 years in our institute are approach in locally advanced cervical cancers [2,3,21], 67%, 77%, 10% and 12%, respectively. The clinical results toxicity can be considerable. For locally advanced cervical of WPHT concurrent with weekly CDDP following by cancer treated with CCRT, the rates of grade 3 acute toxic- HDR brachytherapy at our institute suggest WPHT is fea- ities for GI effects were 7 - 9% [2,3,23]. For moderate acute sible for locally advanced cervical carcinoma patients. hematologic effects, the happening rate during CCRT was reported from 23% to 37% [2,3,23]. In the current study, Adding more beams would lead to improved conformal- the moderate acute toxicities during CCRT are listed as fol- ity without affecting the value of the objective function low: one (1/10) for diarrhea, three (3/10) for leukopenia [20]. The CI is usually larger than 1, indicating that a por- and one (1/10) for thrombocytopenia. (Additional file 1) Page 5 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 (A) The unifor Figure 1 mity index of helical tomotherapy for 10 patients with locally advanced cervical cancer (A) The uniformity index of helical tomotherapy for 10 patients with locally advanced cervical cancer. (B) The conformal index of helical tomotherapy for with locally advanced cervical cancer. Table 2: Dose-volume histograms statistics for the organs at risk Average ± *S.D. Organ Volume (ml) ± *S.D. Helical tomotherapy Conventional radiotherapy †Decreasing percentage p value Rectum 43.5 ± 18.2 Mean dose 41.3 ± 5.1 Gy 50.9 ± 1.9 Gy 18.9% < 0.01 V50.4 37.2 ± 30.1% 80.8 ± 12.4% 55.6% < 0.01 V40 68.3 ± 20.9% 95.2 ± 4.2% 35.0% < 0.01 V30 82.2 ± 15.3% 98.4 ± 2.6% 16.6% < 0.01 Bladder 59.8 ± 24.2 Mean dose 40.5 ± 3.5Gy 50.2 ± 2.5Gy 19.3% < 0.01 V50.4 29.5 ± 14.7% 74.4 ± 17.6% 61.3% < 0.01 V45 49.1 ± 13.7% 86.0 ± 11.5% 43.2% < 0.01 V40 57.9 ± 12.6% 91.3 ± 8.5% 36.8% < 0.01 V30 75.7 ± 12.3% 100.0 ± 0% 24.3% < 0.01 Intestine 1523.3 ± 1389.4 Mean dose 25.1 ± 2.4Gy 34.2 ± 4.2Gy 26.3% < 0.01 V50.4 0.4 ± 0.4% 20.0 ± 10.7% 98.2% < 0.01 V40 4.9 ± 3.2% 33.3 ± 13.1% 84.1% < 0.01 V30 23.5 ± 11.9% 59.5 ± 10.4% 61.1% < 0.01 V20 69.2 ± 10.9% 86.6 ± 8.0% 20.1% < 0.01 Right femur 114.4 ± 16.2 V30 15.5 ± 14.2% 23.2 ± 29.1% 19.0% 0.47 Left femur 114.3 ± 14.0 V30 16.1 ± 13.9% 22.3 ± 28.5% 12.9% 0.54 Left pelvic bone 187.3 ± 19.4 V10 99.9 ± 0.1% 93.1 ± 4.8% -6.8% < 0.01 V20 79.1 ± 4.6% 86.2 ± 5.6% 8.2% < 0.01 Right pelvic bone 189.4 ± 20.1 V10 99.9 ± 0.1% 95.5 ± 2.1% -4.4% < 0.01 V20 78.3 ± 4.8% 89.2 ± 3.1% 12.2% < 0.01 *S.D.: standard deviation. † Decreasing percentage: (conventional radiotherapy - helical tomotherapy)/conventional radiotherapy Page 6 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 and rectum is 25 - 40% and 40 - 57%, 65 - 86% and 88 - 97%, 74 - 84% and 87 - 95%, respectively [24-27]. (Addi- tional file 2) Compared with previous reports, HT decreases 80 - 88% of V40 and 40 - 60% of V30 for the intestine, 11 - 33% of V40 and 14 - 22% of V30 for the bladder and 8 - 19% of V40 and 6 - 14% of V30 for the rec- tum than previous IMRT reports, respectively. It also notes that HT decreases 35% of V45 for the intestine than previ- ous IMRT reports simultaneously. In other words, HT pro- vides significantly superiority for decreasing high dose to these OARs than IMRT does. Therefore, we suggest when treating the locally advanced cervical cancer patients with HT, the optimization constraints of V40 and V30 for the intestine, bladder and rectum could be reconsidered as 5% and 24%, 58% and 76%, 68% and 82%, respectively. HT can deliver dose to bone marrow exactly in total mar- row irradiation and reduce the dose to OARs around 51%- 74% when compared with total body irradiation [13]. It implies that HT can manage bone marrow precisely, either targeting or sparing. Brixey et al. [8] reported that acute hematological toxicity was reduced with pelvic IMRT compared with four-field box techniques in gyneco- Dose-volu si whole pelvic helica <80% pa Figure 2 mi ris lar PTV and o replanning whole pelvic ns me histog intes l tomot ram of tine do hpelvic bon er seapy a helical tomotherapy for com- for o nn d g e e pati ma iving V1 rrow ent with o 0 < 90%, V20 under r the iginal logic cancer patients undergoing chemotherapy. Mell et al. Dose-volume histogram of pelvic bone marrow [28] also provided evidence of an association between the under the similar PTV and intestine dose for one volume of pelvic BM receiving low-dose radiation (V10, patient with original whole pelvic helical tomother- V20) and pointed out the potential of bone marrow spar- apy and giving V10 < 90%, V20 <80% replanning ing-IMRT could diminish the chronic effects of RT on BM whole pelvic helical tomotherapy for comparisons. suppression, improving chemotherapy tolerance. In our study, the pelvic bones sparing technique did not perform The acute toxicities of GI and GU for locally advanced cer- in the original WPHT plan and the value of V10 for pelvic vical cancer treated by WPHT are feasible however the bones almost achieving 100% was noted. In our retro- dominant hematologic toxicities are noted in the current spective data, 40% of acute moderate hematological tox- study. The late moderate toxicities for locally advanced icities happened in the CCRT and 10% of subacute cervical cancer patients treated with CCRT that reported thrombocytopenia was noted in the following days. It is by previous series are 9.4 - 13% for GI effects and 3 - noted that the highly conformal doses distribute to target 14.5% for genitourinary effects [5,21,23]. In the current and large off-target low dose existing simultaneously in study, the subacute grade 3 toxicity is only 1 (10%) for the HT plan. If we target pelvic bone marrow according to thrombocytopenia and there are none with GI and GU Brixey et al. [8] and set pelvic bone marrow optimal con- effects. (Additional file 1) Compared with WPRT, WPHT straints directly, HT can provide as much bone marrow decreases the mean dose to rectum, bladder and intestines sparing in the low dose as we desired. (Fig. 2) Since June successfully. In addition, the V50 decreasing percentage first, the following cervical cancer patients in our center for WPHT in rectum, bladder and intestine is 56%, 61% were performed pelvic bone sparing technique with and 98%, respectively. (Table 2) From the view of physics, WPHT. Up to day, three locally advanced cervical cancer WPHT decreases the mean and high doses to the OARs patients completed the treatment by WPHT concurrent entirely when compared with conventional technique and with chemotherapy and only grade 1 or 2 acute hemato- these physic properties of WPHT reflect the declining rate logic toxicities during CCRT are noted. The encouraging of acute and subacute toxicities for gastrointestinal and results hints that targeting pelvic bones and setting opti- genitourinary events successfully. (Additional file 1) mal constraint for pelvic bones can potentially decrease the acute and subacute clinical toxicities when use WPHT. There are numbers of groups that explored how IMRT can minimize the gastrointestinal, genitourinary and bone There are some limitations in our current study. First, the marrow toxicity than conventional RT for gynecologic small case number and the retrospective study design cancer patients. When using IMRT techniques for gyneco- make any statistical conclusions very tentative. Second, logic treatment, V40 and V30 for the intestine, bladder the follow-up time is short so the long-term results need Page 7 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 to keep closely follow-up. Third, we do not perform pelvic References 1. Sundar SS, Horne A, Kehoe S: Cervical cancer. Clin Evid (Online) bones sparing within this study perhaps this is the reason 2008, 2008:0818. for acute hematologic toxicities dominant therefore enroll 2. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, more patients by limiting bone marrow radiation dose Clarke-Pearson DL, Insalaco S: Concurrent cisplatin-based radi- otherapy and chemotherapy for locally advanced cervical with WPHT technique in the future to confirm our obser- cancer. N Engl J Med 1999, 340:1144-53. vation is warranted. 3. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY: Randomized compar- ison of fluorouracil plus cisplatin versus hydroxyurea as an Conclusions adjunct to radiation therapy in stage IIB-IVA carcinoma of To sum up, whole pelvic helical tomotherapy provides the cervix with negative para-aortic lymph nodes: a Gyneco- logic Oncology Group and Southwest Oncology Group feasible clinical results in patients with locally advanced study. J Clin Oncol 1999, 17:1339-48. cervical carcinoma. Long-term follow-up and to enroll 4. John M, Flam M, Caplan R, Rotman M, Quivey J, Steinfeld A, Russell more locally advanced cervical carcinoma patients by lim- A: Final results of a phase II chemoradiation protocol for locally advanced cervical cancer: RTOG 85-15. Gynecol Oncol iting bone marrow radiation dose with WPHT technique 1996, 61:221-26. is warranted. 5. Tan LT, Zahra M: Long-term survival and late toxicity after chemoradiotherapy for cervical cancer--the Addenbrooke's experience. Clin Oncol (R Coll Radiol) 2008, 20:358-64. Competing interests 6. Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming We have no personal or financial conflict of interest and G, Roeske JC: Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol have not entered into any agreement that could interfere Phys 2002, 52:1330-37. with our access to the data on the research, or upon our 7. Portelance L, Chao KS, Grigsby PW, Bennet H, Low D: Intensity- ability to analyze the data independently, to prepare man- modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer uscripts, and to publish them. receiving pelvic and para-aortic irradiation. Int J Radiat Oncol Biol Phys 2001, 51:261-66. 8. Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ: Authors' contributions Impact of intensity-modulated radiotherapy on acute hema- All authors read and approved the final manuscript. CHH tologic toxicity in women with gynecologic malignancies. Int and PWS carried out all CT evaluations, study design, tar- J Radiat Oncol Biol Phys 2002, 54:1388-96. 9. Lujan AE, Mundt AJ, Yamada SD, Rotmensch J, Roeske JC: Intensity- get delineations and interpretation of the study. CHH modulated radiotherapy as a means of reducing dose to drafted the manuscript. MCW, SMH and CAC took care of bone marrow in gynecologic patients receiving whole pelvic cervical cancer patients. HYL made the treatment plan- radiotherapy. Int J Radiat Oncol Biol Phys 2003, 57:516-21. 10. Ahmed RS, Kim RY, Duan J, Meleth S, De Los Santos JF, Fiveash JB: ning and carried out all WPHT and WPRT comparisons IMRT dose escalation for positive para-aortic lymph nodes in and evaluations. THT and YJC participated in manuscript patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. Int J Radiat preparation and study design. LYW and YPH gave advice Oncol Biol Phys 2004, 60:505-12. on the work and carried out statistical analysis. 11. Bunt L van de, Heide UA van der, Ketelaars M, de Kort GA, Jurgen- liemk-Schulz IM: Conventional, conformal, and intensity-mod- ulated radiation therapy treatment planning of external Additional material beam radiotherapy for cervical cancer: The impact of tumor regression. Int J Radiat Oncol Biol Phys 2006, 64:189-96. 12. Shueng PW, Wu LJ, Chen SY, Hsiao CH, Tien HJ, Cheng PW, Kuo YS, Additional file 1 Chen YJ, Chen CA, Hsieh PY, Hsieh CH: Concurrent Chemoradi- ation Therapy with Helical Tomotherapy for Oropharyngeal Acute and subacute toxicity for locally advanced cervical cancer Cancer - A Preliminary Result. Int J Radiat Oncol Biol Phys 2009 in patients received chemotherapy concurrent with whole pelvic helical press. tomotherapy followed by brachytherapy. 13. Shueng PW, Lin SC, Chong NS, Lee HY, Tien HJ, Wu LJ, Chen CA, Click here for file Lee JJ, Hsieh CH: Total marrow irradiation with helical tomo- [http://www.biomedcentral.com/content/supplementary/1748- therapy for bone marrow transplantation of multiple mye- loma: first experience in Asia. Technol Cancer Res Treat 2009, 717X-4-62-S1.DOC] 8:29-38. 14. Esthappan J, Chaudhari S, Santanam L, Mutic S, Olsen J, Macdonald Additional file 2 DM, Low DA, Singh AK, Grigsby PW: Prospective clinical trial of The rate of cervical carcinoma treated with concurrent chemoradia- positron emission tomography/computed tomography image-guided intensity-modulated radiation therapy for cer- tion using helical tomotherapy at the Far Eastern Memorial Hospital vical carcinoma with positive para-aortic lymph nodes. Int J (FEMH) compared with selected published series. Radiat Oncol Biol Phys 2008, 72:1134-39. Click here for file 15. Benedet JL: Editorial. Int J Gynaecol Obstet 2000, 70:207-08. [http://www.biomedcentral.com/content/supplementary/1748- 16. ICRU: International Commission on Radiation Units and 717X-4-62-S2.DOC] Measurements (ICRU). Prescribing, recording, and reporting photon beam therapy, ICRU report 50: Bethesda, MD: ICRU 1993 [http:// www.oxfordjournals.org/jicru/backissues/reports.html]. 17. ICRU: International Commission on Radiation Units and Measurements (ICRU). Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50), ICRU Report, 62. Acknowledgements Bethesda, MD: ICRU 1999 [http://www.oxfordjournals.org/jicru/back We are indebted to Wei-Hsiang Kung, M.S. for the data collection. issues/reports.html]. 18. Forrest LJ, Mackie TR, Ruchala K, Turek M, Kapatoes J, Jaradat H, Hui S, Balog J, Vail DM, Mehta MP: The utility of megavoltage com- Page 8 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 puted tomography images from a helical tomotherapy sys- tem for setup verification purposes. Int J Radiat Oncol Biol Phys 2004, 60:1639-44. 19. ICRU: International Commission on Radiation Units and Measurements (ICRU). Dose and volume specification for reporting intracavitary therapy in gynecology, ICRU Report, 38. Bethesda, MD: ICRU 1985 [http://www.oxfordjournals.org/jicru/backissues/reports.html]. 20. Wang X, Zhang X, Dong L, Liu H, Gillin M, Ahamad A, Ang K, Mohan R: Effectiveness of noncoplanar IMRT planning using a paral- lelized multiresolution beam angle optimization method for paranasal sinus carcinoma. Int J Radiat Oncol Biol Phys 2005, 63:594-601. 21. Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG: Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irra- diation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol 2004, 22:872-80. 22. Chen ZY, Ma YB, Sheng XG, Zhang XL, Xue L, Song QQ, Liu NF, Miao HQ: [Intensity modulated radiation therapy for patients with gynecological malignancies after hysterectomy and chemotherapy/radiotherapy]. Zhonghua Zhong Liu Za Zhi 2007, 29:305-08. 23. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rot- man M, Gershenson DM, Mutch DG: Pelvic radiation with con- current chemotherapy compared with pelvic and para- aortic radiation for high-risk cervical cancer. N Engl J Med 1999, 340:1137-43. 24. Georg P, Georg D, Hillbrand M, Kirisits C, Potter R: Factors influ- encing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies. Radiother Oncol 2006, 80:19-26. 25. Menkarios C, Azria D, Laliberte B, Moscardo CL, Gourgou S, Leman- ski C, Dubois JB, Ailleres N, Fenoglietto P: Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans. Radiat Oncol 2007, 2:41. 26. Mell LK, Tiryaki H, Ahn KH, Mundt AJ, Roeske JC, Aydogan B: Dosi- metric comparison of bone marrow-sparing intensity-modu- lated radiotherapy versus conventional techniques for treatment of cervical cancer. Int J Radiat Oncol Biol Phys 2008, 71:1504-10. 27. Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ: Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2000, 48:1613-21. 28. Mell LK, Kochanski JD, Roeske JC, Haslam JJ, Mehta N, Yamada SD, Hurteau JA, Collins YC, Lengyel E, Mundt AJ: Dosimetric predic- tors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol Biol Phys 2006, 66:1356-65. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 9 of 9 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

Loading next page...
 
/lp/springer-journals/whole-pelvic-helical-tomotherapy-for-locally-advanced-cervical-cancer-G9rf4USi7Z
Publisher
Springer Journals
Copyright
Copyright © 2009 by Hsieh et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology; Radiotherapy
eISSN
1748-717X
DOI
10.1186/1748-717X-4-62
pmid
20003321
Publisher site
See Article on Publisher Site

Abstract

Background: To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Methods: Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). Results: The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease- free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. Conclusion: HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long- term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted. Page 1 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 Background Methods Cervical cancer is the second most frequent cancer among Patient's characteristics Between November 1st, 2006 to May 31, 2009, 10 women worldwide [1]. It has demonstrated the superior- ity of combined chemotherapy with radiotherapy (RT) in patients undergoing whole pelvic HT (WPHT) for locally the treatment of advanced cervix cancer [2,3]. The radia- advanced cervical cancer without pelvic or paraarotic lym- tion therapy consists of external beam irradiation to the phadenopathy at Far Eastern Memorial Hospital (FEMH) primary tumor and corresponding region of lymphatic were retrospectively enrolled. Staging investigations drainage, followed by brachytherapy to boost the gross included complete history and physical examination, tumor in the cervix. A significant benefit of chemoradia- fiberoptic endoscopic evaluation, complete blood counts, tion on both overall survival and progress-free survival liver and renal function tests, chest X-ray, magnetic reso- rate was mentioned [4]. However, grade 3 or 4 haemato- nance imaging (MRI) scans or computed tomography logical (white cell count, 16% vs. 8%; platelets, 1·5% vs. (CT) scans of the pelvic region. The disease was staged 0·2%; haematological not otherwise specified, 29% vs. according to the International Federation of Gynecology 1%) and gastrointestinal toxicities (9% vs. 4%) signifi- and Obstetrics (FIGO) criteria [15]. cantly greater in the concomitant chemoradiation group than the RT alone group should also be mentioned. Tan et Radiotherapy al. [5] also proposed a late toxicity observation for con- Radiotherapy was administered to the whole pelvic region comitant chemoradiation of locally advanced cervical in 28 fractions totaling 50.4 Gy followed by intracavitary cancer. There were 14.5%, 9.4% and 11.4% for grade 3 or brachytherapy. The total dose of brachytherapy delivered 4 urinary, bowel and affecting other organs complica- was 30 Gy/6 fractions in patients. The total dose delivered tions, respectively. to point A (a reference location 2 cm lateral and 2 cm superior to the cervical os) was 80.4 Gy in patients; the With the advances in radiotherapy modalities, whole pel- total dose delivered to point p (the pelvic wall) was 55.0 vic intensity-modulated radiotherapy (WP-IMRT) applied Gy in patients. Cisplatin (CDDP) was administered dur- to gynecologic malignancies with excellent planning tar- ing external radiation, beginning on the first day of radia- get volume (PTV) coverage and is associated with less tion for 5 weeks concurrent with WPHT. A dose of 40 mg/ CDDP (maximum dose, 70 mg) was used and admin- acute gastrointestinal sequelae than conventional whole m pelvic radiotherapy (WPRT) as reported by Mundt et al. istered via a peripheral vein to patients. [6]. Under similar target coverage, IMRT is superior to conventional techniques in normal tissue sparing for the Immobilization treatment of cervical cancer and a number of groups have A BlueBAG™ immobilization system (Medical Intelli- explored IMRT in the gynecologic setting as a method to gence, Schwabmünchen, Germany) was used for each of minimize the gastrointestinal, genitourinary, and bone these patients to fix pelvic and extremities. Positioning marrow toxicity that occurs in conventional RT [7-11]. was supine with arms up, and feet placed in an ankle holder. All patients underwent a CT planning scan with Helical tomotherapy (HT) is a new CT-based rotational our departmental scanner (Siemens Somatom Plus 4 CT intensity modulated radiotherapy and provides an scanner) from the diaphragm to 5 cm below the ischial impressive ability for highly conformal dose distributions tuberosities. Localization marks were placed on anterior and simultaneous critical organ sparing ability [12,13]. and lateral sides of the patients at the mid-plane and mid- HT is being tested to apply for gynecologic malignancies line at the level of L4-L5 vertebral body interspace. CT recently and provides encouraging results about excellent with 5-mm slice thickness was taken for treatment plan- setup accuracy and reducing margins for the external ning. Target objects and normal structures were contoured beam treatment of gynecologic malignancies [14]. How- on a Pinnacle3 treatment planning system (Philips ever, this report did not provide the clinical results about Healthcare, Madison, Wisconsin, USA). The MRI or CT the gynecologic malignancies treated by HT. images were retrieved on a Pinnacle workstation and fused with the CT images for contouring of the tumor vol- In our institute, a Tomotherapy Hi-Art system (Tomother- ume. apy, Inc., Madison, Wisconsin, USA) was installed and used for treatment from November 2006. We report here Delineation of target volumes our initial clinical 2 years experience for patients with Delineation and constraints was according to Radiation locally advanced cervical cancer with HT, focusing on the Therapy Oncology Group (RTOG) 0418 protocol and the correlation between dosimetry, clinical outcome and early International Commission on Radiation Units and Meas- toxicities. urements reports 50 [16] and 62 [17] recommendations. The Gross Tumor Volume (GTV) was defined as all known Page 2 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 gross disease determined from CT, clinical information, as follows: small bowel (2 cm above the most superior and MRI. The Clinical Target Volume (CTV) was defined vessel contour) < 30% to receive ≥ 40 Gy, minor deviation as areas considered containing potential microscopic dis- 30% to 40 Gy; Rectum < 60% to receive ≥ 30 Gy, minor ease. Internal Target Volume (ITV) was defined as the vol- deviation 35% to 50 Gy; Bladder < 35% to receive ≥ 45 ume of the vagina and paravaginal soft tissues that is in Gy, minor deviation 35% to 50 Gy; Femoral head ≤ 15% both the empty and full bladder CT scans that were done to receive ≥ 30 Gy, minor deviation 20% to 30 Gy. at the time of simulation and fused together. The Planning Target Volume (PTV) would provide a 7 mm margin Intracavitary brachytherapy (anteriorly, posteriorly, laterally, as well as in the superior An iridium-192 (high-dose-rate) source was used with and inferior directions) around the nodal CTV and ITV. standard Fletcher-Suit-Delclos intracavitary applicators. The treatment plan would be done on the full bladder Patients were treated twice a week after WPHT completed scan. The treatment plan used for each patient would be for 3 weeks, with a prescribed dose of 500 cGy per fraction based on an analysis of the volumetric dose, including to Point A. The high-dose rate (HDR) source dwell times dose volume histogram (DVH) analyses of the PTV and were manually calculated based on our institutional sys- critical normal structures. The GTV plus a 7-mm expan- tem of empiric intracavitary irradiation rules. Postimplan- sion was defined as the primary tumor CTV to account for tation dosimetry was performed with the GENIE microscopic spread, excluding the bowel, bladder, and treatment planning system v1.0.4 (Nucletron, Nether- rectum if they were not clinically involved); The nodal land), and included calculation of dose to the "classical" CTV should include the internal (hypogastric and obtura- Point A bilaterally (a reference location 2 cm lateral and 2 tor), external, common iliac lymph nodes perinodal tis- cm superior to the cervical os), pelvic sidewall bilaterally sue, pertinent clips and down to the level of S3. (Point P, defined as the point 2 cm above the top of the Identification of the CTV usually began with the identifi- colpostat and 6 cm lateral to midline), and the rectal cation of the iliac vessels. The average margin would be 7 point and bladder point as defined by the International mm. Bone and intraperitoneal small bowel should be Commission on Radiation Units and Measurements [19]. excluded from the CTV; also, iliopsoas muscle that lies For each implant, point doses to Points A and P, the blad- adjacent to clinically negative lymph nodes should also be der point, and the rectal point were recorded; after com- excluded from the CTV. Approximately 1.5 cm of tissue pletion of therapy, the doses for the six implants were anterior to the S1, S2 and S3 sacral segments was usually summed. There is no standard or universally accepted added to the CTV in order to include the presacral lymph fraction size for HDR brachytherapy. At our institution we nodes and uterosacral ligaments. The most antero-lateral have chosen to use the fraction size of 500 cGy. external iliac lymph nodes that lied just proximal to the inguinal canal should be excluded from the CTV. The CTV Conventional treatment planning for comparison of the nodes should end 7 mm from L4/L5 interspace to Conventional whole pelvic radiation therapy (WPRT) account for the PTV. The PTV for nodes stopped at L4/L5 plans were generated using Pinnacle3 treatment planning interspace. The vaginal and parametrial CTV should actu- system (Philips Healthcare, Madison, Wisconsin, USA). ally be an ITV, which will account for internal organ The isocenter was placed at the geometric center of the motion. The inferior limit was usually around the level of PTV. A 4-field "box" plan was designed using 6-MV pho- the upper third of the symphysis pubis but could be indi- tons with apertures shaped to the PTV in each beam's eye- vidualized based on inferior spread of the patient's tumor. view. The pelvic field extended from the upper margin of The lateral margin of the vaginal PTV should be to the L5 to the midportion of the obturator foramen or the low- obturator muscle. However, at least 3 cm of the vagina est level of disease, with a 2-cm margin, and laterally 1.5 needed to be treated or at least 1 cm below the obturator cm beyond the lateral margins of the bony pelvic wall (at foramen. The 90% isodose surface covered between 95% least 7 cm from the midline). For the lateral fields, the and 98% of the PTV 50.4, or volumes of overdose exceed anterior border was the pubic symphysis and the posterior 115% < 5% of the PTV 50.4 volume could be considered border was the space between S2 and S3. The fields could acceptable. The field width, pitch, and modulation factor be modified to include areas of known tumor and wedges (MF) usually used for the WPHT treatment planning opti- were used as needed. All plans were normalized to cover mization were 2.5 cm, 0.32 and 3.0, respectively. All 98% of the PTV with 50.4 Gy. The 2% underdose repre- patients received daily megavoltage computed tomogra- sents those voxels at the periphery. This normalization phy (MVCT) acquisitions for setup verification [18]. provided conformal coverage while minimizing dose nonuniformity within the target. Normal structures will be contoured using the full-blad- der CT scan. The OARs (i.e., bladder, rectum, sigmoid, Dose-volume analysis of treatment plans small bowel, and femoral heads) were contoured as solid Dose-volume histograms (DVHs) of the PTVs and the crit- organs. Dose-volume constraints for normal tissues were ical normal structures were analyzed accordingly. For Page 3 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 PTVs, we evaluated the volume, the volume covered by survival was calculated from the date of pathologic proof 95% of the prescription dose (V95), and the minimum to the date of the first physical or radiographic evidence of ) and 95% (D ) of the PTV. The doses delivered to 5% (D disease progression, death, or the last follow-up visit. Sur- 5 95 critical organs with functional subunits organized in a vival was calculated from the date of pathologic proof to series were examined. The conformal index (CI) and the the date of death or the last follow-up visit. All analyses uniformity index (UI) had been used to evaluate the con- were performed using the Statistical Package for the Social formity and uniformity of the plan. The volume received Sciences, version 12.0 (SPSS, Chicago, IL, USA). the mean dose for PTV generated from the DVH. The con- formal index (CI) for PTV was calculated using the for- Results mula CI = V /V , where V was the ratio of the Patient characteristics ICRU TV PTV TV treated volume enclosed by the prescription isodose sur- Ten women were included. They had a median age of 58 face and V was the planning target volume [17]. The years (range, 33-72 years). All belong to FIGO Stage IIB PTV uniformity index (UI) was defined as UI = D /D , where and IIIB. The medium tumor volume was 45.9 cm . The 5 95 D and D were the minimum doses delivered to 5% and medium weekly cycles of chemotherapy were 5 weeks. 5 95 95% of the PTV reported previously [20]. Seventy percent of patients could complete 4 weekly cycles of chemotherapy. All of the patients were treated Toxicity with definitively concurrent chemotherapy with WPHT Interruptions in radiotherapy might be necessitated by followed by brachytherapy. (Table 1) uncontrolled diarrhea, or other acute complications. If radiation therapy was held, then chemotherapy would Treatment outcome also be held. Chemotherapy stopped at the completion of The mean survival was 25 months (range, 3 to 27 RT. If chemotherapy was held, radiation therapy would months). The actuarial 2-year overall survival, progress- continue. Radiation was only stopped in cases of grade 4 free survival, locoregional control and distant metastasis- hematologic or non-hematologic toxicity until toxicity free rates were 67%, 77%, 90% and 88%, respectively. The resolved to at least grade 3. CDDP was withheld in any 2-year survival, progression-free, locoregional-progres- case involving grade 3 toxicity until the toxicity regressed sion-free and distant metastasis-free patient number over to any grade of <3; in patients with grade 3 toxicity that all patients are 9/10, 8/10, 9/10 and 9/10, respectively. persisted >2 weeks, chemotherapy was no longer admin- Ninety percent of patients were surviving at the time of istered. this report. Follow-up Dose-volume analysis and comparison for WPHT and Upon treatment completion, patients were evaluated WPRT every 3 months for the first year, every 4 months during The WPHT for UI and CI was 1.07 ± 0.05 and 1.01 ± 0.05, the second year, every 6 months during the third year, and respectively. The UI and CI for individual patient are plot- annually thereafter. At each visit, a physical and pelvic ted in Figures 1A and 1B, respectively. Dose-volume histo- examination, blood counts, clinical chemistry, and chest grams statistics for the organs at risk are described in table x-rays were performed. Computed tomography (CT) scan, 2. WPHT provided better critical organs sparing than ultrasound (US), and other imaging studies were con- WPRT in the mean dose and the other parameters for rec- ducted when appropriate. Suspected cases of persistent or tum, bladder and intestine with a statistically significant recurrent disease were confirmed by biopsy whenever pos- level (p value < 0.01), respectively. WPHT provided sible. Acute and late toxicities (occurring >90 days after impressive ability of high dose declining for OARs than beginning RT) were defined and graded according to the WPRT. However, WPHT had poorer results for right and Common Terminology Criteria for Adverse Events v3.0 left side pelvic bone sparing than WPRT due to lacking of (CTCAE v3.0). V10 and V20 constraint for planning initially. Statistical methods Acute and subacute toxicity Descriptive statistics (mean, median, proportions) were Acute toxicity of radiation therapy within chemotherapy calculated to characterize the patient, disease, and treat- and late toxicity is detailed in Additional file 1. One grade ment features as well as toxicities after treatment. The 3 of acute toxicity for diarrhea, thrombocytopenia and overall survival (OS), progression-free survival (PFS), three grade 3 of leucopenia were noted during CCRT. locoregional progression-free (LRPF), and distant metas- Only one grade 3 of subacute toxicity for thrombocytope- tases-free (DMF) rates were estimated using the Kaplan- nia was noted. There was no grade 3 or 4 subacute toxici- Meier product-limit method. Progression was defined as a ties for anemia, leucopenia, genitourinary or 50 percent increase in the product of the two largest diam- gastrointestinal. eters of the primary tumor or metastasis. Progression-free Page 4 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 Table 1: Patient characteristics Variable No. of patient (%) Age (years) Median (range) 58 (33-72) Gender Female 10 (100%) Karnofsky performance status < 70 0 ≥ 70 10 (100%) Pathology Squamous cell carcinoma 7 (70%) Adenocarcinoma 3 (30%) International Federation of Gynecology and Obstetrics (FIGO) stage Stage IIB 9 (90%) Stage IIIB 1 (10%) Tumor size Medium length (range) 5.5 cm (4.3 - 8.4 cm) Medium depth (range) 3.7 cm (2.4 - 4.6 cm) Medium width (range) 4.4 cm (3.5 - 6.0 cm) Weekly cycles of chemotherapy 5 weeks 5 (50%) 4 weeks 2 (20%) 3 weeks 1 (10%) 2 weeks 2 (20%) tion of the prescription dose was delivered outside the Discussion In our preliminary results of locally advanced cervical can- PTV. The greater the CI, the less is the dose conformity to cer receiving WPHT concurrent with chemotherapy fol- the PTV [20]. The greater UI indicates higher heterogene- lowed by brachytherapy, HT provides feasible outcomes ity in the PTV [22]. In the current study, the UI and CI for and acceptable toxicity during and after CCRT. WPHT was 1.07 ± 0.05 and 1.01 ± 0.05, respectively. WPHT provides the impressed conformality and uniform- The 2-year estimate of OS, PFS, locoregional failure only ity for locally advanced cervical carcinoma patients. The and distant metastasis only rate in the RT plus weekly UI and CI for individual patient are described in Fig. 1A CDDP reported by randomized trials was 67 - 71%, 64 - and 1B, respectively. 84%, 10 - 25% and 6 - 11%, respectively [2,3,21]. The overall survival, disease-free survival, locoregional failure Despite the clear efficacy of a combined modality and distant metastasis rate at 2 years in our institute are approach in locally advanced cervical cancers [2,3,21], 67%, 77%, 10% and 12%, respectively. The clinical results toxicity can be considerable. For locally advanced cervical of WPHT concurrent with weekly CDDP following by cancer treated with CCRT, the rates of grade 3 acute toxic- HDR brachytherapy at our institute suggest WPHT is fea- ities for GI effects were 7 - 9% [2,3,23]. For moderate acute sible for locally advanced cervical carcinoma patients. hematologic effects, the happening rate during CCRT was reported from 23% to 37% [2,3,23]. In the current study, Adding more beams would lead to improved conformal- the moderate acute toxicities during CCRT are listed as fol- ity without affecting the value of the objective function low: one (1/10) for diarrhea, three (3/10) for leukopenia [20]. The CI is usually larger than 1, indicating that a por- and one (1/10) for thrombocytopenia. (Additional file 1) Page 5 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 (A) The unifor Figure 1 mity index of helical tomotherapy for 10 patients with locally advanced cervical cancer (A) The uniformity index of helical tomotherapy for 10 patients with locally advanced cervical cancer. (B) The conformal index of helical tomotherapy for with locally advanced cervical cancer. Table 2: Dose-volume histograms statistics for the organs at risk Average ± *S.D. Organ Volume (ml) ± *S.D. Helical tomotherapy Conventional radiotherapy †Decreasing percentage p value Rectum 43.5 ± 18.2 Mean dose 41.3 ± 5.1 Gy 50.9 ± 1.9 Gy 18.9% < 0.01 V50.4 37.2 ± 30.1% 80.8 ± 12.4% 55.6% < 0.01 V40 68.3 ± 20.9% 95.2 ± 4.2% 35.0% < 0.01 V30 82.2 ± 15.3% 98.4 ± 2.6% 16.6% < 0.01 Bladder 59.8 ± 24.2 Mean dose 40.5 ± 3.5Gy 50.2 ± 2.5Gy 19.3% < 0.01 V50.4 29.5 ± 14.7% 74.4 ± 17.6% 61.3% < 0.01 V45 49.1 ± 13.7% 86.0 ± 11.5% 43.2% < 0.01 V40 57.9 ± 12.6% 91.3 ± 8.5% 36.8% < 0.01 V30 75.7 ± 12.3% 100.0 ± 0% 24.3% < 0.01 Intestine 1523.3 ± 1389.4 Mean dose 25.1 ± 2.4Gy 34.2 ± 4.2Gy 26.3% < 0.01 V50.4 0.4 ± 0.4% 20.0 ± 10.7% 98.2% < 0.01 V40 4.9 ± 3.2% 33.3 ± 13.1% 84.1% < 0.01 V30 23.5 ± 11.9% 59.5 ± 10.4% 61.1% < 0.01 V20 69.2 ± 10.9% 86.6 ± 8.0% 20.1% < 0.01 Right femur 114.4 ± 16.2 V30 15.5 ± 14.2% 23.2 ± 29.1% 19.0% 0.47 Left femur 114.3 ± 14.0 V30 16.1 ± 13.9% 22.3 ± 28.5% 12.9% 0.54 Left pelvic bone 187.3 ± 19.4 V10 99.9 ± 0.1% 93.1 ± 4.8% -6.8% < 0.01 V20 79.1 ± 4.6% 86.2 ± 5.6% 8.2% < 0.01 Right pelvic bone 189.4 ± 20.1 V10 99.9 ± 0.1% 95.5 ± 2.1% -4.4% < 0.01 V20 78.3 ± 4.8% 89.2 ± 3.1% 12.2% < 0.01 *S.D.: standard deviation. † Decreasing percentage: (conventional radiotherapy - helical tomotherapy)/conventional radiotherapy Page 6 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 and rectum is 25 - 40% and 40 - 57%, 65 - 86% and 88 - 97%, 74 - 84% and 87 - 95%, respectively [24-27]. (Addi- tional file 2) Compared with previous reports, HT decreases 80 - 88% of V40 and 40 - 60% of V30 for the intestine, 11 - 33% of V40 and 14 - 22% of V30 for the bladder and 8 - 19% of V40 and 6 - 14% of V30 for the rec- tum than previous IMRT reports, respectively. It also notes that HT decreases 35% of V45 for the intestine than previ- ous IMRT reports simultaneously. In other words, HT pro- vides significantly superiority for decreasing high dose to these OARs than IMRT does. Therefore, we suggest when treating the locally advanced cervical cancer patients with HT, the optimization constraints of V40 and V30 for the intestine, bladder and rectum could be reconsidered as 5% and 24%, 58% and 76%, 68% and 82%, respectively. HT can deliver dose to bone marrow exactly in total mar- row irradiation and reduce the dose to OARs around 51%- 74% when compared with total body irradiation [13]. It implies that HT can manage bone marrow precisely, either targeting or sparing. Brixey et al. [8] reported that acute hematological toxicity was reduced with pelvic IMRT compared with four-field box techniques in gyneco- Dose-volu si whole pelvic helica <80% pa Figure 2 mi ris lar PTV and o replanning whole pelvic ns me histog intes l tomot ram of tine do hpelvic bon er seapy a helical tomotherapy for com- for o nn d g e e pati ma iving V1 rrow ent with o 0 < 90%, V20 under r the iginal logic cancer patients undergoing chemotherapy. Mell et al. Dose-volume histogram of pelvic bone marrow [28] also provided evidence of an association between the under the similar PTV and intestine dose for one volume of pelvic BM receiving low-dose radiation (V10, patient with original whole pelvic helical tomother- V20) and pointed out the potential of bone marrow spar- apy and giving V10 < 90%, V20 <80% replanning ing-IMRT could diminish the chronic effects of RT on BM whole pelvic helical tomotherapy for comparisons. suppression, improving chemotherapy tolerance. In our study, the pelvic bones sparing technique did not perform The acute toxicities of GI and GU for locally advanced cer- in the original WPHT plan and the value of V10 for pelvic vical cancer treated by WPHT are feasible however the bones almost achieving 100% was noted. In our retro- dominant hematologic toxicities are noted in the current spective data, 40% of acute moderate hematological tox- study. The late moderate toxicities for locally advanced icities happened in the CCRT and 10% of subacute cervical cancer patients treated with CCRT that reported thrombocytopenia was noted in the following days. It is by previous series are 9.4 - 13% for GI effects and 3 - noted that the highly conformal doses distribute to target 14.5% for genitourinary effects [5,21,23]. In the current and large off-target low dose existing simultaneously in study, the subacute grade 3 toxicity is only 1 (10%) for the HT plan. If we target pelvic bone marrow according to thrombocytopenia and there are none with GI and GU Brixey et al. [8] and set pelvic bone marrow optimal con- effects. (Additional file 1) Compared with WPRT, WPHT straints directly, HT can provide as much bone marrow decreases the mean dose to rectum, bladder and intestines sparing in the low dose as we desired. (Fig. 2) Since June successfully. In addition, the V50 decreasing percentage first, the following cervical cancer patients in our center for WPHT in rectum, bladder and intestine is 56%, 61% were performed pelvic bone sparing technique with and 98%, respectively. (Table 2) From the view of physics, WPHT. Up to day, three locally advanced cervical cancer WPHT decreases the mean and high doses to the OARs patients completed the treatment by WPHT concurrent entirely when compared with conventional technique and with chemotherapy and only grade 1 or 2 acute hemato- these physic properties of WPHT reflect the declining rate logic toxicities during CCRT are noted. The encouraging of acute and subacute toxicities for gastrointestinal and results hints that targeting pelvic bones and setting opti- genitourinary events successfully. (Additional file 1) mal constraint for pelvic bones can potentially decrease the acute and subacute clinical toxicities when use WPHT. There are numbers of groups that explored how IMRT can minimize the gastrointestinal, genitourinary and bone There are some limitations in our current study. First, the marrow toxicity than conventional RT for gynecologic small case number and the retrospective study design cancer patients. When using IMRT techniques for gyneco- make any statistical conclusions very tentative. Second, logic treatment, V40 and V30 for the intestine, bladder the follow-up time is short so the long-term results need Page 7 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 to keep closely follow-up. Third, we do not perform pelvic References 1. Sundar SS, Horne A, Kehoe S: Cervical cancer. Clin Evid (Online) bones sparing within this study perhaps this is the reason 2008, 2008:0818. for acute hematologic toxicities dominant therefore enroll 2. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, more patients by limiting bone marrow radiation dose Clarke-Pearson DL, Insalaco S: Concurrent cisplatin-based radi- otherapy and chemotherapy for locally advanced cervical with WPHT technique in the future to confirm our obser- cancer. N Engl J Med 1999, 340:1144-53. vation is warranted. 3. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY: Randomized compar- ison of fluorouracil plus cisplatin versus hydroxyurea as an Conclusions adjunct to radiation therapy in stage IIB-IVA carcinoma of To sum up, whole pelvic helical tomotherapy provides the cervix with negative para-aortic lymph nodes: a Gyneco- logic Oncology Group and Southwest Oncology Group feasible clinical results in patients with locally advanced study. J Clin Oncol 1999, 17:1339-48. cervical carcinoma. Long-term follow-up and to enroll 4. John M, Flam M, Caplan R, Rotman M, Quivey J, Steinfeld A, Russell more locally advanced cervical carcinoma patients by lim- A: Final results of a phase II chemoradiation protocol for locally advanced cervical cancer: RTOG 85-15. Gynecol Oncol iting bone marrow radiation dose with WPHT technique 1996, 61:221-26. is warranted. 5. Tan LT, Zahra M: Long-term survival and late toxicity after chemoradiotherapy for cervical cancer--the Addenbrooke's experience. Clin Oncol (R Coll Radiol) 2008, 20:358-64. Competing interests 6. Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming We have no personal or financial conflict of interest and G, Roeske JC: Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol have not entered into any agreement that could interfere Phys 2002, 52:1330-37. with our access to the data on the research, or upon our 7. Portelance L, Chao KS, Grigsby PW, Bennet H, Low D: Intensity- ability to analyze the data independently, to prepare man- modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer uscripts, and to publish them. receiving pelvic and para-aortic irradiation. Int J Radiat Oncol Biol Phys 2001, 51:261-66. 8. Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ: Authors' contributions Impact of intensity-modulated radiotherapy on acute hema- All authors read and approved the final manuscript. CHH tologic toxicity in women with gynecologic malignancies. Int and PWS carried out all CT evaluations, study design, tar- J Radiat Oncol Biol Phys 2002, 54:1388-96. 9. Lujan AE, Mundt AJ, Yamada SD, Rotmensch J, Roeske JC: Intensity- get delineations and interpretation of the study. CHH modulated radiotherapy as a means of reducing dose to drafted the manuscript. MCW, SMH and CAC took care of bone marrow in gynecologic patients receiving whole pelvic cervical cancer patients. HYL made the treatment plan- radiotherapy. Int J Radiat Oncol Biol Phys 2003, 57:516-21. 10. Ahmed RS, Kim RY, Duan J, Meleth S, De Los Santos JF, Fiveash JB: ning and carried out all WPHT and WPRT comparisons IMRT dose escalation for positive para-aortic lymph nodes in and evaluations. THT and YJC participated in manuscript patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. Int J Radiat preparation and study design. LYW and YPH gave advice Oncol Biol Phys 2004, 60:505-12. on the work and carried out statistical analysis. 11. Bunt L van de, Heide UA van der, Ketelaars M, de Kort GA, Jurgen- liemk-Schulz IM: Conventional, conformal, and intensity-mod- ulated radiation therapy treatment planning of external Additional material beam radiotherapy for cervical cancer: The impact of tumor regression. Int J Radiat Oncol Biol Phys 2006, 64:189-96. 12. Shueng PW, Wu LJ, Chen SY, Hsiao CH, Tien HJ, Cheng PW, Kuo YS, Additional file 1 Chen YJ, Chen CA, Hsieh PY, Hsieh CH: Concurrent Chemoradi- ation Therapy with Helical Tomotherapy for Oropharyngeal Acute and subacute toxicity for locally advanced cervical cancer Cancer - A Preliminary Result. Int J Radiat Oncol Biol Phys 2009 in patients received chemotherapy concurrent with whole pelvic helical press. tomotherapy followed by brachytherapy. 13. Shueng PW, Lin SC, Chong NS, Lee HY, Tien HJ, Wu LJ, Chen CA, Click here for file Lee JJ, Hsieh CH: Total marrow irradiation with helical tomo- [http://www.biomedcentral.com/content/supplementary/1748- therapy for bone marrow transplantation of multiple mye- loma: first experience in Asia. Technol Cancer Res Treat 2009, 717X-4-62-S1.DOC] 8:29-38. 14. Esthappan J, Chaudhari S, Santanam L, Mutic S, Olsen J, Macdonald Additional file 2 DM, Low DA, Singh AK, Grigsby PW: Prospective clinical trial of The rate of cervical carcinoma treated with concurrent chemoradia- positron emission tomography/computed tomography image-guided intensity-modulated radiation therapy for cer- tion using helical tomotherapy at the Far Eastern Memorial Hospital vical carcinoma with positive para-aortic lymph nodes. Int J (FEMH) compared with selected published series. Radiat Oncol Biol Phys 2008, 72:1134-39. Click here for file 15. Benedet JL: Editorial. Int J Gynaecol Obstet 2000, 70:207-08. [http://www.biomedcentral.com/content/supplementary/1748- 16. ICRU: International Commission on Radiation Units and 717X-4-62-S2.DOC] Measurements (ICRU). Prescribing, recording, and reporting photon beam therapy, ICRU report 50: Bethesda, MD: ICRU 1993 [http:// www.oxfordjournals.org/jicru/backissues/reports.html]. 17. ICRU: International Commission on Radiation Units and Measurements (ICRU). Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50), ICRU Report, 62. Acknowledgements Bethesda, MD: ICRU 1999 [http://www.oxfordjournals.org/jicru/back We are indebted to Wei-Hsiang Kung, M.S. for the data collection. issues/reports.html]. 18. Forrest LJ, Mackie TR, Ruchala K, Turek M, Kapatoes J, Jaradat H, Hui S, Balog J, Vail DM, Mehta MP: The utility of megavoltage com- Page 8 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:62 http://www.ro-journal.com/content/4/1/62 puted tomography images from a helical tomotherapy sys- tem for setup verification purposes. Int J Radiat Oncol Biol Phys 2004, 60:1639-44. 19. ICRU: International Commission on Radiation Units and Measurements (ICRU). Dose and volume specification for reporting intracavitary therapy in gynecology, ICRU Report, 38. Bethesda, MD: ICRU 1985 [http://www.oxfordjournals.org/jicru/backissues/reports.html]. 20. Wang X, Zhang X, Dong L, Liu H, Gillin M, Ahamad A, Ang K, Mohan R: Effectiveness of noncoplanar IMRT planning using a paral- lelized multiresolution beam angle optimization method for paranasal sinus carcinoma. Int J Radiat Oncol Biol Phys 2005, 63:594-601. 21. Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG: Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irra- diation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol 2004, 22:872-80. 22. Chen ZY, Ma YB, Sheng XG, Zhang XL, Xue L, Song QQ, Liu NF, Miao HQ: [Intensity modulated radiation therapy for patients with gynecological malignancies after hysterectomy and chemotherapy/radiotherapy]. Zhonghua Zhong Liu Za Zhi 2007, 29:305-08. 23. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rot- man M, Gershenson DM, Mutch DG: Pelvic radiation with con- current chemotherapy compared with pelvic and para- aortic radiation for high-risk cervical cancer. N Engl J Med 1999, 340:1137-43. 24. Georg P, Georg D, Hillbrand M, Kirisits C, Potter R: Factors influ- encing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies. Radiother Oncol 2006, 80:19-26. 25. Menkarios C, Azria D, Laliberte B, Moscardo CL, Gourgou S, Leman- ski C, Dubois JB, Ailleres N, Fenoglietto P: Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans. Radiat Oncol 2007, 2:41. 26. Mell LK, Tiryaki H, Ahn KH, Mundt AJ, Roeske JC, Aydogan B: Dosi- metric comparison of bone marrow-sparing intensity-modu- lated radiotherapy versus conventional techniques for treatment of cervical cancer. Int J Radiat Oncol Biol Phys 2008, 71:1504-10. 27. Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ: Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2000, 48:1613-21. 28. Mell LK, Kochanski JD, Roeske JC, Haslam JJ, Mehta N, Yamada SD, Hurteau JA, Collins YC, Lengyel E, Mundt AJ: Dosimetric predic- tors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol Biol Phys 2006, 66:1356-65. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 9 of 9 (page number not for citation purposes)

Journal

Radiation OncologySpringer Journals

Published: Dec 10, 2009

References