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Craniospinal irradiation in the treatment of chemotherapy refractory leptomeningeal metastasis from breast cancer: A case report

Craniospinal irradiation in the treatment of chemotherapy refractory leptomeningeal metastasis... INTRODUCTIONLeptomeningeal metastasis (LM) is a relatively uncommon development in solid tumors, however, when it does occur, its consequences are associated with significant morbidity and mortality.1 LM is defined as tumor cell invasion of the pia, arachnoid mater, subarachnoid space or cerebrospinal fluid.2 The incidence of LM from solid tumors is approximately 10%,3 with breast cancer contributing to the majority of all LM cases (12–64% of cases) followed by lung cancer and melanoma.4–6 The incidence appears to be increasing as improvement of systemic and local therapies increase patient overall survival.7,8 Despite improvements in therapy, morbidity from LM disease itself and the toxicities from treatment, remain significant. Symptoms of the disease are variable and may include cranial nerve palsies, encephalopathy, seizures, radiculopathies, incontinence or motor deficiencies.9 The median survival for patients with LM is abysmal, ranging between 4 and 15 weeks with only 15% of patients being alive at 1 year.10–12Robust treatment guidelines for LM do not exist because of poor prognosis, relatively low numbers and a lack of large randomized clinical data in the literature.13,14 Radiation therapy has been shown to improve quality of life, although, its effects are often short lived.15–18Although palliative radiation is often indicated for patients with LM, the role of craniospinal irradiation (CSI) is less defined. Most commonly, the recommendation in the literature is to avoid CSI for the treatment of LM except for select cases.19,20 There is sparse data to support these recommendations, especially given the tremendous advancements in radiation therapy technology and techniques.We present a case of a woman suffering from LM with excellent response to CSI and survival well above the median despite minimal response to intrathecal therapy.CASE REPORTMrs. M. is a 50‐year‐old woman with a history of metastatic breast cancer who presented with a 2‐week history of headaches, nausea, and vomiting. History and physical exam revealed no photophobia or focal neurologic deficits, however, generalized lower extremity weakness reduced her ability to ambulate significantly below baseline. Considering her history of metastatic breast cancer, a magnetic resonance imaging of the brain was ordered which showed a stable or slightly reduced size of a previously treated lesion in the left insular cortex. Given the ongoing symptoms, lumbar puncture with CSF cytology was performed, which confirmed metastatic carcinoma consistent with breast primary, establishing a diagnosis of LM.Mrs. M had been diagnosed 12 years prior with a T2 N0 multicentric lobular breast carcinoma at the age of 38. She was treated with lumpectomy, axillary lymph node dissection followed by completion mastectomy, adjuvant chemotherapy and chest wall radiation. This was followed by 5 years of tamoxifen therapy. Ten and a half years after her initial diagnosis at the age of 48 years, her cancer recurred in her brain and bones. She received stereotactic radiosurgery to a solitary, gradually growing lesion in her left insular cortex. At the same time, she was found to have lesions in her thoracic spine and right scapula. She received a single fraction of radiation to her scapula and was restarted on tamoxifen with excellent response in her thoracic spine. She went just over 1 year without recurrence.Upon her diagnosis of LM, Mrs. M received intrathecal methotrexate and cytarabine with no resolution of her symptoms and persistently positive CSF cytology. She was then switched to six cycles of intrathecal liposomal cytarabine along with oral capecitabine. Despite several cycles of intrathecal and systemic chemotherapy treatments there was no clearance of her CSF cytology and she had only partial resolution of her headaches and nausea. There was no treatable solid tumor identified on CT or MRI imaging of her brain to account for her symptoms.Mrs. M's case was discussed at multidisciplinary tumor boards. Given the persistent positivity on CSF cytology it was decided she would receive palliative CSI to a dose of 36Gy in 20 fractions over 4 weeks time prescribed to cover the anterior spinal canal with 95% of the prescription dose (Figure 1). She had significant toxicities during this treatment, including sore throat, odynophagia, and significant fatigue. Of significance, despite being on a relatively modest dose of dexamethasone, she also developed severe proximal muscle weakness requiring an early and rapid tapering of her steroid. This increased her fatigue, nausea and general malaise on treatment.1FIGURECraniospinal irradiation treatment plan for Mrs. M. showing the 95% isodose line (aqua blue line) covering the whole brain, meninges and the anterior spinal canalFollowing her radiation, her acute side effects rapidly resolved over 4–6 weeks. Her proximal muscle weakness was slower to respond, nonetheless she was ambulating short distances with a walker at 1 month of follow‐up. After 3 months, her strength had almost returned to baseline and she was walking slowly, without assistance. She remained on tamoxifen and received 1 year of oral capecitabine.She did very well for 2 years following her radiation treatment, at which point she developed rapid vision loss and was found to have hydrocephalus requiring a ventriculoperitoneal shunt. Vision and general strength did not fully recover following this and she declined despite the procedure. The cause of her hydrocephalus was never clear but was not aggressively investigated due to the rapid deterioration of the patient's health at this point. Ultimately, she died from her disease 2 years and 11 months following her initial presentation with LM and 2½ years following her CSI (Figure 2).2FIGUREApproximate timeline of Mrs. M's Breast Cancer history, from diagnosis, throughout her treatment and disease progression. Leptomeningeal metastases median survival is indicated for comparison. Ca, cancer; LN, lymph node; adj, adjuvant; T‐spine, thoracic spine; SRS, stereotactic radiosurgery; EBRT, external beamDISCUSSIONChemotherapy, typically intravenous or intrathecally administered, is the first‐line treatment modality for LM disease. However, chemotherapeutic options are limited in LM disease because of the poor blood‐brain barrier penetration of most intravenously or orally administered agents.21–23 The three main agents used intrathecally for LM treatment are methotrexate, cytarabine and thiotepa.24–26 In this case, we have a patient who has disease refractory to standard chemotherapy agents for LM leaving radiation therapy as a salvage palliative therapy.Overall, studies support the inclusion of radiation therapy for the treatment of LM7 although there is not a lot of evidence on the use of CSI. CSI is a method that is used sparingly in the treatment of patients with LM because of its technically complicated set‐up, the overall poor prognosis with LM and the association of CSI with pronounced toxicities such as myelosuppression, mucositis, nausea and dysphagia. Current literature frequently highlights the limited indications of CSI in LM due to its many toxicities and its small documented survival benefit. A review by Le Rhun et al suggested that “focal radiotherapy is commonly indicated for macroscopic disease,” while the role of whole brain radiation therapy “is decreasing,” and CSI “is rarely an option for LM from solid cancers” because of the risk of side effects.8 The National Comprehensive Cancer Network (NCCN) guidelines for LM suggest giving stereotactic radiation, surgery, involved field or whole brain radiation therapy to bulky disease, neurologically symptomatic or painful sites. It states, CSI should only otherwise be considered in “highly select patients [with radiosensitive disease] (e.g., leukemia, lymphoma).”20Four retrospective reports in the literature examine series of patients with LM treated with CSI.27–30 All studies concluded that CSI is feasible and effective in select patients. They suggested overall survival with CSI in their cohorts to be similar to that of other patient cohorts treated without CSI but with palliation of symptoms achieved. Combined modality therapy seemed superior to irradiation alone. El Shafie et al showed on multivariate analysis that age, performance status and neurologic response to therapy predicted longer overall survival. In this study, 3 of 25 patients survived past 1 year and one patient survived for over 2 years.29 In a more recent study by Devecka et al, it was demonstrated that patients had a better overall survival (median of 7.3 months compared to 1.5 months) with both a Karnofsky performance scale index of >70% and the absence of extra‐central nervous system disease.27 This suggests there may be a LM subpopulation that benefits from CSI.Recently, Yang et al reported a Phase I prospective trial using hypofractionated proton CSI for the treatment of LM disease. Twenty‐four patients were enrolled with the median progression‐free survival being 7 months and overall survival being 8 months. Four patients were alive and free from central nervous system progression for more than 12 months. The authors reported that adverse effects from proton CSI are far less prevalent than for what is reported for traditional photon CSI.31 While this study uses a different radiation modality than was used in our patient, it further suggests that in select patients CSI can result in prolonger survival.We report here a case of a patient who received craniospinal radiation for LM and survived 2 years and 11 months, a time well above the median stated in the literature, with a reasonable quality of life. This was despite no response to intrathecal chemotherapy. To our knowledge, this is the first case reported with long‐term survival following treatment of LM with salvage CSI. This was a patient that was relatively young, had minor neurological symptoms from her disease and was refractory to chemotherapy. This may represent a sub‐population with LM that benefits from CSI. Caution in patient selection is still required, however, due to the significant acute side effects of CSI. There are remarkably few recent studies in the literature examining the expansion of the therapeutic role of CSI for LM, highlighting the need for further inquiry.CONCLUSIONWith improving radiation and systemic therapies, newer data is required to revisit the LM treatment paradigm. Despite a declining use and lack of mention in guidelines and review, the use of CSI for LM can have good survival and quality of life outcomes for certain patients despite potentially severe acute toxicities on treatment. CSI should be considered in LM from solid tumors, particularly in younger patients with good performance status and potentially in patients who have failed intra‐thecal chemotherapy. More research is required to determine the subpopulations of patients who might benefit most from CSI.CONFLICT OF INTERESTThe authors declare no conflict of interest.AUTHOR'S CONTRIBUTIONSMethodology, Writing—Original Draft, Writing—Review and Editing, D.T.; Writing—Review and Editing, D.V.; Conceptualization, Methodology, Writing—Review and Editing, Supervision, Project Administration, K.R.ETHICAL STATEMENTThis report was waived for review by the Thunder Bay Regional Health Sciences Centre Ethics Review Board. Formal decision on August 5, 2021. Written consent was obtained from next of kin to publish the above information.DATA AVAILABILITY STATEMENTData sharing is not applicable to this article as no new data were created or analyzed in this study.REFERENCESBlaney SM, Poplack DG. Neoplastic meningitis: diagnosis and treatment considerations. Med Oncol Northwood Lond Engl. 2000;17(3):151‐162. doi:10.1007/bf02780522Chamberlain MC. Leptomeningeal metastasis. Curr Opin Oncol. 2010;22(6):627‐635. doi:10.1097/CCO.0b013e32833de986Le Rhun E, Weller M, Brandsma D, et al. EANO–ESMO clinical practice guidelines for diagnosis, treatment and follow‐up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. 2017;28:iv84‐iv99. doi:10.1093/annonc/mdx221Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982;49(4):759‐772. doi:10.1002/1097‐0142(19820215)49:4<759::aid‐cncr2820490427>3.0.co;2‐7Joshi A, Ghosh J, Noronha V, Parikh P, Prabhash K. Leptomeningeal metastasis in solid tumors with a special focus on lung cancer. Indian J Cancer. 2014;51(4):410‐413. doi:10.4103/0019‐509X.175351Shapiro WR, Posner JB, Ushio Y, Chemik NL, Young DF. Treatment of meningeal neoplasms. Cancer Treat Rep. 1977;61(4):733‐743.Buszek SM, Chung C. Radiotherapy in Leptomeningeal disease: a systematic review of randomized and non‐randomized trials. Front Oncologia. 2019;9. doi:10.3389/fonc.2019.01224Le Rhun E, Preusser M, van den Bent M, Andratschke N, Weller M. How we treat patients with leptomeningeal metastases. ESMO Open. 2019;4(suppl 2):e000507. doi:10.1136/esmoopen‐2019‐000507Chamberlain MC. Carcinomatous meningitis. Arch Neurol. 1997;54(1):16‐17. doi:10.1001/archneur.1997.00550130008003Le Rhun E, Taillibert S, Zairi F, et al. A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol. 2013;113(1):83‐92. doi:10.1007/s11060‐013‐1092‐8Jo J‐C, Kang MJ, Kim JE, et al. Clinical features and outcome of leptomeningeal metastasis in patients with breast cancer: a single center experience. Cancer Chemother Pharmacol. 2013;72(1):201‐207. doi:10.1007/s00280‐013‐2185‐yRudnicka H, Niwińska A, Murawska M. Breast cancer leptomeningeal metastasis—the role of multimodality treatment. J Neurooncol. 2007;84(1):57‐62. doi:10.1007/s11060‐007‐9340‐4Niwińska A, Pogoda K, Michalski W, Kunkiel M, Jagiełło‐Gruszfeld A. Determinants of prolonged survival for breast cancer patient groups with leptomeningeal metastasis (LM). J Neurooncol. 2018;138(1):191‐198. doi:10.1007/s11060‐018‐2790‐zKapke JT, Schneidewend RJ, Jawa ZA, Huang C‐C, Connelly JM, Chitambar CR. High‐dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: case series and review of the literature. Hematol Oncol Stem Cell Ther. 2019;12(4):189‐193. doi:10.1016/j.hemonc.2019.08.008Bruno MK, Raizer J. Leptomeningeal metastases from solid tumors (meningeal carcinomatosis). Cancer Treat Res. 2005;125:31‐52. doi:10.1007/0‐387‐24199‐x_3Niwińska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival. Med Oncol Northwood Lond Engl. 2013;30(1):408. doi:10.1007/s12032‐012‐0408‐4Owonikoko TK, Arbiser J, Zelnak A, et al. Current approaches to the treatment of metastatic brain tumours. Nat Rev Clin Oncol. 2014;11(4):203‐222. doi:10.1038/nrclinonc.2014.25Niwińska A, Rudnicka H, Murawska M. Breast cancer Leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal Cytarabine as intra–cerebrospinal fluid chemotherapy. Clin Breast Cancer. 2015;15(1):66‐72. doi:10.1016/j.clbc.2014.07.004Assi HI, Mahmoud T, Saadeh FS, El Darsa H. Management of leptomeningeal metastasis in breast cancer. Clin Neurol Neurosurg. 2018;172:151‐159. doi:10.1016/j.clineuro.2018.07.001NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines[R]). Central Nervous System Cancers; 2020. Accessed September 13, 2020. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdfDeng Y, Feng W, Wu J, et al. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non‐small‐cell lung cancer. Mol Clin Oncol. 2014;2(1):116‐120. doi:10.3892/mco.2013.190Hoffknecht P, Tufman A, Wehler T, et al. Efficacy of the irreversible ErbB family blocker Afatinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)–pretreated non–small‐cell lung cancer patients with brain metastases or Leptomeningeal disease. J Thorac Oncol. 2015;10(1):156‐163. doi:10.1097/JTO.0000000000000380Togashi Y, Masago K, Masuda S, et al. Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non‐small cell lung cancer. Cancer Chemother Pharmacol. 2012;70(3):399‐405. doi:10.1007/s00280‐012‐1929‐4Chahal J, Stopeck A, Clarke K, Livingston RB, Chalasani P. Intravenous thiotepa for treatment of breast cancer‐related leptomeningeal carcinomatosis: case series. Neurol Sci off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2015;36(9):1691‐1693. doi:10.1007/s10072‐015‐2259‐1Glantz MJ, Van Horn A, Fisher R, Chamberlain MC. Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer. 2010;116(8):1947‐1952. doi:10.1002/cncr.24921Le Rhun E, Wallet J, Mailliez A, et al. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer. Neuro‐Oncol. 2019;22:524‐538. doi:10.1093/neuonc/noz201Devecka M, Duma MN, Wilkens JJ, et al. Craniospinal irradiation (CSI) in patients with leptomeningeal metastases: risk‐benefit‐profile and development of a prognostic score for decision making in the palliative setting. BMC Cancer. 2020;20(1):501. doi:10.1186/s12885‐020‐06984‐1Hermann B, Hültenschmidt B, Sautter‐Bihl ML. Radiotherapy of the neuroaxis for palliative treatment of leptomeningeal carcinomatosis. Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al. 2001;177(4):195‐199. doi:10.1007/pl00002398El Shafie RA, Böhm K, Weber D, et al. Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis. Cancer Manag Res. 2019;11:789‐801. doi:10.2147/CMAR.S182154Schiopu S, Habl G, Haefner M, et al. Helical tomotherapy in patients with leptomeningeal metastases. Cancer Manag Res. 2018;11:401‐409. doi:10.2147/CMAR.S185414Yang TJ, Wijetunga NA, Yamada J, et al. Clinical trial of proton craniospinal irradiation for leptomeningeal metastases. Neuro‐Oncol. 2021;23(1):134‐143. doi:10.1093/neuonc/noaa152 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Reports Wiley

Craniospinal irradiation in the treatment of chemotherapy refractory leptomeningeal metastasis from breast cancer: A case report

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Abstract

INTRODUCTIONLeptomeningeal metastasis (LM) is a relatively uncommon development in solid tumors, however, when it does occur, its consequences are associated with significant morbidity and mortality.1 LM is defined as tumor cell invasion of the pia, arachnoid mater, subarachnoid space or cerebrospinal fluid.2 The incidence of LM from solid tumors is approximately 10%,3 with breast cancer contributing to the majority of all LM cases (12–64% of cases) followed by lung cancer and melanoma.4–6 The incidence appears to be increasing as improvement of systemic and local therapies increase patient overall survival.7,8 Despite improvements in therapy, morbidity from LM disease itself and the toxicities from treatment, remain significant. Symptoms of the disease are variable and may include cranial nerve palsies, encephalopathy, seizures, radiculopathies, incontinence or motor deficiencies.9 The median survival for patients with LM is abysmal, ranging between 4 and 15 weeks with only 15% of patients being alive at 1 year.10–12Robust treatment guidelines for LM do not exist because of poor prognosis, relatively low numbers and a lack of large randomized clinical data in the literature.13,14 Radiation therapy has been shown to improve quality of life, although, its effects are often short lived.15–18Although palliative radiation is often indicated for patients with LM, the role of craniospinal irradiation (CSI) is less defined. Most commonly, the recommendation in the literature is to avoid CSI for the treatment of LM except for select cases.19,20 There is sparse data to support these recommendations, especially given the tremendous advancements in radiation therapy technology and techniques.We present a case of a woman suffering from LM with excellent response to CSI and survival well above the median despite minimal response to intrathecal therapy.CASE REPORTMrs. M. is a 50‐year‐old woman with a history of metastatic breast cancer who presented with a 2‐week history of headaches, nausea, and vomiting. History and physical exam revealed no photophobia or focal neurologic deficits, however, generalized lower extremity weakness reduced her ability to ambulate significantly below baseline. Considering her history of metastatic breast cancer, a magnetic resonance imaging of the brain was ordered which showed a stable or slightly reduced size of a previously treated lesion in the left insular cortex. Given the ongoing symptoms, lumbar puncture with CSF cytology was performed, which confirmed metastatic carcinoma consistent with breast primary, establishing a diagnosis of LM.Mrs. M had been diagnosed 12 years prior with a T2 N0 multicentric lobular breast carcinoma at the age of 38. She was treated with lumpectomy, axillary lymph node dissection followed by completion mastectomy, adjuvant chemotherapy and chest wall radiation. This was followed by 5 years of tamoxifen therapy. Ten and a half years after her initial diagnosis at the age of 48 years, her cancer recurred in her brain and bones. She received stereotactic radiosurgery to a solitary, gradually growing lesion in her left insular cortex. At the same time, she was found to have lesions in her thoracic spine and right scapula. She received a single fraction of radiation to her scapula and was restarted on tamoxifen with excellent response in her thoracic spine. She went just over 1 year without recurrence.Upon her diagnosis of LM, Mrs. M received intrathecal methotrexate and cytarabine with no resolution of her symptoms and persistently positive CSF cytology. She was then switched to six cycles of intrathecal liposomal cytarabine along with oral capecitabine. Despite several cycles of intrathecal and systemic chemotherapy treatments there was no clearance of her CSF cytology and she had only partial resolution of her headaches and nausea. There was no treatable solid tumor identified on CT or MRI imaging of her brain to account for her symptoms.Mrs. M's case was discussed at multidisciplinary tumor boards. Given the persistent positivity on CSF cytology it was decided she would receive palliative CSI to a dose of 36Gy in 20 fractions over 4 weeks time prescribed to cover the anterior spinal canal with 95% of the prescription dose (Figure 1). She had significant toxicities during this treatment, including sore throat, odynophagia, and significant fatigue. Of significance, despite being on a relatively modest dose of dexamethasone, she also developed severe proximal muscle weakness requiring an early and rapid tapering of her steroid. This increased her fatigue, nausea and general malaise on treatment.1FIGURECraniospinal irradiation treatment plan for Mrs. M. showing the 95% isodose line (aqua blue line) covering the whole brain, meninges and the anterior spinal canalFollowing her radiation, her acute side effects rapidly resolved over 4–6 weeks. Her proximal muscle weakness was slower to respond, nonetheless she was ambulating short distances with a walker at 1 month of follow‐up. After 3 months, her strength had almost returned to baseline and she was walking slowly, without assistance. She remained on tamoxifen and received 1 year of oral capecitabine.She did very well for 2 years following her radiation treatment, at which point she developed rapid vision loss and was found to have hydrocephalus requiring a ventriculoperitoneal shunt. Vision and general strength did not fully recover following this and she declined despite the procedure. The cause of her hydrocephalus was never clear but was not aggressively investigated due to the rapid deterioration of the patient's health at this point. Ultimately, she died from her disease 2 years and 11 months following her initial presentation with LM and 2½ years following her CSI (Figure 2).2FIGUREApproximate timeline of Mrs. M's Breast Cancer history, from diagnosis, throughout her treatment and disease progression. Leptomeningeal metastases median survival is indicated for comparison. Ca, cancer; LN, lymph node; adj, adjuvant; T‐spine, thoracic spine; SRS, stereotactic radiosurgery; EBRT, external beamDISCUSSIONChemotherapy, typically intravenous or intrathecally administered, is the first‐line treatment modality for LM disease. However, chemotherapeutic options are limited in LM disease because of the poor blood‐brain barrier penetration of most intravenously or orally administered agents.21–23 The three main agents used intrathecally for LM treatment are methotrexate, cytarabine and thiotepa.24–26 In this case, we have a patient who has disease refractory to standard chemotherapy agents for LM leaving radiation therapy as a salvage palliative therapy.Overall, studies support the inclusion of radiation therapy for the treatment of LM7 although there is not a lot of evidence on the use of CSI. CSI is a method that is used sparingly in the treatment of patients with LM because of its technically complicated set‐up, the overall poor prognosis with LM and the association of CSI with pronounced toxicities such as myelosuppression, mucositis, nausea and dysphagia. Current literature frequently highlights the limited indications of CSI in LM due to its many toxicities and its small documented survival benefit. A review by Le Rhun et al suggested that “focal radiotherapy is commonly indicated for macroscopic disease,” while the role of whole brain radiation therapy “is decreasing,” and CSI “is rarely an option for LM from solid cancers” because of the risk of side effects.8 The National Comprehensive Cancer Network (NCCN) guidelines for LM suggest giving stereotactic radiation, surgery, involved field or whole brain radiation therapy to bulky disease, neurologically symptomatic or painful sites. It states, CSI should only otherwise be considered in “highly select patients [with radiosensitive disease] (e.g., leukemia, lymphoma).”20Four retrospective reports in the literature examine series of patients with LM treated with CSI.27–30 All studies concluded that CSI is feasible and effective in select patients. They suggested overall survival with CSI in their cohorts to be similar to that of other patient cohorts treated without CSI but with palliation of symptoms achieved. Combined modality therapy seemed superior to irradiation alone. El Shafie et al showed on multivariate analysis that age, performance status and neurologic response to therapy predicted longer overall survival. In this study, 3 of 25 patients survived past 1 year and one patient survived for over 2 years.29 In a more recent study by Devecka et al, it was demonstrated that patients had a better overall survival (median of 7.3 months compared to 1.5 months) with both a Karnofsky performance scale index of >70% and the absence of extra‐central nervous system disease.27 This suggests there may be a LM subpopulation that benefits from CSI.Recently, Yang et al reported a Phase I prospective trial using hypofractionated proton CSI for the treatment of LM disease. Twenty‐four patients were enrolled with the median progression‐free survival being 7 months and overall survival being 8 months. Four patients were alive and free from central nervous system progression for more than 12 months. The authors reported that adverse effects from proton CSI are far less prevalent than for what is reported for traditional photon CSI.31 While this study uses a different radiation modality than was used in our patient, it further suggests that in select patients CSI can result in prolonger survival.We report here a case of a patient who received craniospinal radiation for LM and survived 2 years and 11 months, a time well above the median stated in the literature, with a reasonable quality of life. This was despite no response to intrathecal chemotherapy. To our knowledge, this is the first case reported with long‐term survival following treatment of LM with salvage CSI. This was a patient that was relatively young, had minor neurological symptoms from her disease and was refractory to chemotherapy. This may represent a sub‐population with LM that benefits from CSI. Caution in patient selection is still required, however, due to the significant acute side effects of CSI. There are remarkably few recent studies in the literature examining the expansion of the therapeutic role of CSI for LM, highlighting the need for further inquiry.CONCLUSIONWith improving radiation and systemic therapies, newer data is required to revisit the LM treatment paradigm. Despite a declining use and lack of mention in guidelines and review, the use of CSI for LM can have good survival and quality of life outcomes for certain patients despite potentially severe acute toxicities on treatment. CSI should be considered in LM from solid tumors, particularly in younger patients with good performance status and potentially in patients who have failed intra‐thecal chemotherapy. More research is required to determine the subpopulations of patients who might benefit most from CSI.CONFLICT OF INTERESTThe authors declare no conflict of interest.AUTHOR'S CONTRIBUTIONSMethodology, Writing—Original Draft, Writing—Review and Editing, D.T.; Writing—Review and Editing, D.V.; Conceptualization, Methodology, Writing—Review and Editing, Supervision, Project Administration, K.R.ETHICAL STATEMENTThis report was waived for review by the Thunder Bay Regional Health Sciences Centre Ethics Review Board. Formal decision on August 5, 2021. Written consent was obtained from next of kin to publish the above information.DATA AVAILABILITY STATEMENTData sharing is not applicable to this article as no new data were created or analyzed in this study.REFERENCESBlaney SM, Poplack DG. Neoplastic meningitis: diagnosis and treatment considerations. Med Oncol Northwood Lond Engl. 2000;17(3):151‐162. doi:10.1007/bf02780522Chamberlain MC. Leptomeningeal metastasis. Curr Opin Oncol. 2010;22(6):627‐635. doi:10.1097/CCO.0b013e32833de986Le Rhun E, Weller M, Brandsma D, et al. EANO–ESMO clinical practice guidelines for diagnosis, treatment and follow‐up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. 2017;28:iv84‐iv99. doi:10.1093/annonc/mdx221Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982;49(4):759‐772. doi:10.1002/1097‐0142(19820215)49:4<759::aid‐cncr2820490427>3.0.co;2‐7Joshi A, Ghosh J, Noronha V, Parikh P, Prabhash K. Leptomeningeal metastasis in solid tumors with a special focus on lung cancer. Indian J Cancer. 2014;51(4):410‐413. doi:10.4103/0019‐509X.175351Shapiro WR, Posner JB, Ushio Y, Chemik NL, Young DF. Treatment of meningeal neoplasms. Cancer Treat Rep. 1977;61(4):733‐743.Buszek SM, Chung C. Radiotherapy in Leptomeningeal disease: a systematic review of randomized and non‐randomized trials. Front Oncologia. 2019;9. doi:10.3389/fonc.2019.01224Le Rhun E, Preusser M, van den Bent M, Andratschke N, Weller M. How we treat patients with leptomeningeal metastases. ESMO Open. 2019;4(suppl 2):e000507. doi:10.1136/esmoopen‐2019‐000507Chamberlain MC. Carcinomatous meningitis. Arch Neurol. 1997;54(1):16‐17. doi:10.1001/archneur.1997.00550130008003Le Rhun E, Taillibert S, Zairi F, et al. A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol. 2013;113(1):83‐92. doi:10.1007/s11060‐013‐1092‐8Jo J‐C, Kang MJ, Kim JE, et al. Clinical features and outcome of leptomeningeal metastasis in patients with breast cancer: a single center experience. Cancer Chemother Pharmacol. 2013;72(1):201‐207. doi:10.1007/s00280‐013‐2185‐yRudnicka H, Niwińska A, Murawska M. Breast cancer leptomeningeal metastasis—the role of multimodality treatment. 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Journal

Cancer ReportsWiley

Published: Jul 1, 2022

Keywords: breast cancer; craniospinal irradiation; leptomeningeal metastasis

References