A systematic review and meta-analysis of the impact of radiation-related lymphopenia on outcomes in pancreatic cancer.

Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of 5-10%. Radiation is commonly used in neoadjuvant and adjuvant settings to improve local control. Studies have shown that circulating lymphocyte count depletion after radiation has been associated with poor tumor control and inferior overall survival (OS) outcomes. Method: To better understand the impact of radiation-associated lymphopenia in pancreatic cancer, the authors undertook this systematic review and meta-analysis of clinical studies that have reported radiation-related lymphopenia in pancreatic cancer. Results: A systematic methodology search of PubMed, Embase and the Cochrane Library resulted in 2969 abstracts. Nine studies fulfilled the inclusion criteria. Six studies reported on outcomes in patients undergoing definitive chemoradiation and three studies comparing outcomes in stereotactic body radiotherapy versus definitive chemoradiation. The patients with severe lymphopenia were at increased risk of death with a pooled hazard ratio of 2.33 (95% CI: 1.79, 3.03; I2: 36%; p < 0.001) compared with patients with no severe lymphopenia. The odds of developing severe lymphopenia were 1.12 (95% CI: 0.45, 2.79; I2: 95%; p < 0.81). The pooled mean difference for OS was -6.80 months (95% CI: -10.35, -3.24; I2: 99%; p < 0.002), suggesting that patients who develop grade 3 or 4 lymphopenia have inferior median OS outcomes. Limiting the mean splenic dose to less than 9 Gy as well as various spleen dosimetric parameters such as visit (V)10 <32%, V15 <23% and V20 <15.4% can reduce the incidence of severe lymphopenia. Conclusion: Radiation-related lymphopenia is associated with an increased hazard of death and inferior median OS. Spleen dosimetric parameters correlate with the incidence of severe lymphopenia and with sub-optimal survival outcomes. There is a need to validate these findings in prospective studies.

The mechanistic rationale of drugs, primary endpoints, geographical distribution of clinical trials against severe acute respiratory syndrome-related coronavirus-2: A systematic review.

There are numerous ongoing studies assessing treatment options for preventing, treating, and managing complications of coronavirus disease-2019 disease. The objective of this study was to do a systematic review and critical appraisal of the ongoing clinical trials with an aim to provide insight into the various interventions tested, clinical rationale, geographical distribution of the trials as well as the endpoints assessed in the studies. ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and PubMed were assessed till 11 May 2020. The search resulted in 3242 ongoing studies of which 829 studies were included. There are 134 different drug-based interventions being assessed in 463 clinical trials as treatment options China accounts for 35% of all ongoing clinical studies followed by USA 23% and other countries together account for 42%. Amongst the 463 studies assessing drug-based treatment options, studies that are funded by federal and academic institutions are 79.6%, pharmaceutical company-funded studies are 15.11%, and no funding information is available in 5.10%. The definitive outcomes like mortality are being assessed as primary outcome in 22.8% of the studies only and need for ventilator in 6.2% of the studies. Amongst the pharmaceutical company-funded drug-based studies, only 20% of the studies had mortality as the primary outcome. Only 5.5% of the ongoing clinical trials are specifically designed to assess the most vulnerable population like elderly, patients with comorbidities and cancer. Multiple intervention-based clinical studies against severe acute respiratory syndrome-related coronavirus-2 are being performed throughout the world with a high concentration of clinical trials in the developed world with concern that of elderly and patients with comorbidities are being underrepresented and definite endpoints like mortality are being assessed in only one-fifth of the studies.

A Systematic Review of Radiation-Related Lymphopenia in Genito-urinary Malignancies.

BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.

A phase III randomised trial of trans-abdominal ultrasound in improving application quality and dosimetry of intra-cavitary brachytherapy in locally advanced cervical cancer.

INTRODUCTION: Intra-cavitary brachytherapy (ICB) remains an integral part of radiotherapy treatment in cervical cancer. Two-dimensional X ray point-based planning remains common and blind insertion leads to uterine perforations and higher toxicity. We conducted a randomised controlled trial of using trans-abdominal ultrasound in performing ICB to reduce perforation and organ at risk doses. PATIENT AND METHODS: The present study is a phase III open label randomised controlled trial of ultrasound guided ICB conducted on invasive cervical cancer patients. Patients were randomised by a simple computer-generated randomization chart into Arm A (No Ultrasound guidance) and Arm B (ICB with ultrasound guidance). The uterine perforation rates, tandem length change rates, bladder doses, rectal dose and procedure times were compared. Fischer exact test was used to compare the arms and p value <0.05 considered significant. RESULTS: A total of 160 patients were randomised. With US assistance, the uterine perforation rate was 1.25% (n = 1). In the non-US assistance arm the perforation rate was 12.5% (n = 10) (p = 0.005). Mean time to complete the entire procedure was significantly shortened from 26 min to 19 min favouring the US arm (p = 0.001). Dosimetric assessment between the two groups showed significant decrease in dose received by the various organs at risk with US assistance. CONCLUSION: The present study confirms significant improvement in application quality as well as dosimetry with reduction in procedure time. Trans-Abdominal US should be routinely used for ICB procedures, particularly in resource limited settings.

Hypofractionated radiotherapy with temozolomide in diffuse intrinsic pontine gliomas: a randomized controlled trial.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is the most common form of brainstem glioma. The present study was performed to assess if hypofractionated radiotherapy completed in < 3 weeks with temozolomide improves survival in DIPG. MATERIAL AND METHODS: The present study is a phase II open label randomized trial. The study included newly diagnosed patients with DIPG. Patients in arm A received conventional fractionated RT of 60 Gy in 30 fractions over 6 weeks while patients in arm B received hypo-fractionated radiotherapy of 39 Gy in 13 fractions over 2.6 weeks along with concurrent Temozolomide (TMZ) 75 mg/m2 from day 1 to day 17 followed by adjuvant TMZ for six cycles. The survival analysis was performed with modified intention to treat analysis. RESULTS: A total of 35 patients were randomized. 33 patients were evaluable. 93% (n = 14) of patients in the conventional arm completed treatment while only 17% (n = 3) of the children could complete planned course of treatment in the experimental arm. The median overall survival (OS) was 11 months (95% CI - 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI - 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity. CONCLUSION: The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. Conventional radiotherapy remains the standard of care.

A systematic review of the role of carbon ion radiation therapy in recurrent rectal cancer.

BACKGROUND: Colorectal cancer is the fourth leading cause of cancer-associated death in the world. The 5-year local recurrence rates in patients undergoing multimodality therapy are approximately 5-10%. The standard approach to treat locally recurrent rectal is re-irradiation followed by surgical resection. Recent reports have suggested that the treatment outcomes with carbon ion radiation therapy (CIRT) in recurrent rectal cancer are promising and have superior results compared to photon therapy. Hence, we performed a systematic review to evaluate the patterns of care and treatment outcomes of recurrent rectal cancer patients treated with CIRT. METHODOLOGY: We performed a systematic search to identify the articles that reported on CIRT use in recurrent rectal cancer. RESULTS: Systematic search of PubMed and Cochrane Central resulted in 98 abstracts. Eight studies fulfilled the predefined inclusion criteria. Among eight studies, one study is a prospective phase I/II study done in Japan; three prospective studies are ongoing (PANDORA-01 trial, HIMAT1351trial, and a phase II study of reirradiation for prior CIRT), and five studies are institutional reports on role of CIRT. These studies were predominantly reported from Japan and Germany. All reports except one were performed in patients who have not received prior radiation. The most commonly utilized treatment prescription was 73.4 Gy (RBE) in 16 fractions over 4 weeks in patients without any prior history of radiation and 36 Gy in 12 fractions over 3 weeks at 3 Gy per fraction in patients with prior photon radiation to the pelvis. There is one ongoing trial assessing the role of carbon ion re-irradiation in patients who had prior CIRT for rectal cancer. CONCLUSION: CIRT holds immense promise in improving outcomes in locally recurrent rectal cancer. There is a need for more multi-institutional prospective clinical trials to assess the role of CIRT.

Impact of surgery, adjuvant treatment, and other prognostic factors in the management of anaplastic ganglioglioma.

BACKGROUND/PURPOSE: Anaplastic ganglioglioma (AGG) is a rare tumor with both glial and neuronal component accounting for less than 1% of all CNS tumors with limited information about the optimum treatment and outcome of these tumors. METHOD AND MATERIALS: We did a thorough search of the PubMed with the following MesH terms: "Ganglioglioma; Anaplastic ganglioglioma; Ganglioglioma AND treatment; and Anaplastic ganglioglioma AND survival" to find all possible publications related to AGG to perform an individual patient data analysis and derive the survival outcome and optimum treatment of these tumors. RESULTS: A total of 56 articles were retrieved pertaining to AGG with 88 patients. However, a total of 40 publications found eligible with 69 patients for individual patient data analysis. Median age for the entire cohort was 16 years (range 0.2-77 years). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), subtotal resection or debulking was reported in 25 cases (39.1%). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), and subtotal resection or debulking was reported in 25 cases (39.1%). Median overall survival (OS) was 29 months [95% CI 15.8-42.2 months] with 2- and 5-year OS 61 and 39.4% respectively. CONCLUSION: AGG is associated with a dismal. Pediatric age and a gross total resection of tumor confer a better progression-free survival and OS. Hence, surgery should remain the cornerstone of therapy. However, because of modest survival, there is enough opportunity to improve survival with addition of adjuvant radiation and chemotherapy. A whole genome sequencing and molecular characterization would help to derive the best treatment option.

Patterns of care and impact of prognostic factors in the outcome of NUT midline carcinoma: a systematic review and individual patient data analysis of 119 cases.

INTRODUCTION: NUT midline carcinoma is a rare tumour occurring in young adults which is frequently misdiagnosed as poorly differentiated squamous cell carcinoma or germ cell tumour. Though considered highly aggressive, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes. METHODS: Two authors independently searched PubMed and Google search for eligible studies from 1950 till July 1 2017 published in English language using MESH terms NUT midline carcinoma; NUT midline carcinoma and radiotherapy and translocation 15:19 tumour. RESULTS: Data of 119 patients were retrieved from 64 publications for statistical analysis. Median age of the entire cohort was 23 years (range 0-68 years). The analysis revealed equal incidence in males and females (60:58). The present analysis revealed that the most common location is the lung (n = 42) followed by head and neck (n = 40). Median OS for the entire cohort was only 5 months with 1 and 5 year OS for the entire cohort was 24.99 and 7.09% respectively. Radiotherapy and chemotherapy inclusion in primary treatment had a significant impact on overall survival on univariate analysis while surgery did not affect survival significantly. No impact on overall survival was found based on type of molecular translocation, i.e., NUT-BRD4, NUT-BRD3 or other variants. Inadequate data were available for identify impact of BET inhibitors and HiDAc on PFS and OS. CONCLUSION: NUT midline carcinoma has dismal prognosis. Radiotherapy and chemotherapy improves survival, but do not provide long term control except in anecdotal cases. Further research is needed to improve outcomes in future.

Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases.

INTRODUCTION: Head and neck extramedullary plasmacytoma is a rare localized plasma cell neoplasm. We intended to perform this review of the published literature to assess the demographic profile, pattern of care and survival outcomes. METHODS: Two authors independently searched PubMed, Google search and Cochrane library for eligible studies from 1950 till July 1, 2016, published in English language. RESULTS: Median age of the cohort was 57 years (range 11-85). Site-wise distributions were paranasal sinuses 22.3% (70), nasal cavity 17.5% (55), nasopharynx 10.8% (34). Median size of SEMP was 3 cm (range 0.3-12 cm). Treatment distribution was radiotherapy (RT) in 52% (164), surgery (S) 19% (60), chemotherapy (C) 5% (16), S + RT 23.49% (74),CRT 1.9% (6), S + C 0.6% (2), S + RT + C 0.95% (3).Radiation was used as a modality in 78.4%(247), surgery in 44.1%(139), chemotherapy in 4.8%(15). Median radiation dose used was 45 Gy with range 20-61 Gy. Median overall survival (OS) was 40 months (range 0.5-298). Median local progression-free survival was 36 months (range 0-298). Median myeloma relapse-free survival was 36 months (range 0.5-298). Five- and 10-year OS was 78.33 and 68.61%. Five-year cause-specific survival (CSS) and 10-year CSS was 90.15 and 83.31%. Five-year LPFS was 94.78%, and 10-year LPFS was 88.43%. Five-year myeloma progression-free survival was 84.46%, and 10-year myeloma PFS was 80.44%. The factors associated with risk of local relapse were site of disease (sinonasal), secretory EMP, type of treatment received (surgery + RT > RT alone > surgery on univariate analysis). Risk factors for myeloma relapse were coexisting diseases, site of disease (sinonasal), bony erosion, size of lesion > 5 cm and type of treatment received on univariate analysis. CONCLUSION: Our study shows that combined modality S + RT is superior compared to uni-modality in preventing local recurrence. Radiation dose of 45 Gy is optimal. Nodal irradiation has no impact on local recurrence.

Pattern of care and impact of prognostic factors in the outcome of ameloblastic carcinoma: a systematic review and individual patient data analysis of 199 cases.

Ameloblastic carcinoma is a rare locally aggressive odontogenic neoplasm. These tumors are most commonly found to arise from mandible. Because of rarity, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes. Two authors independently searched PubMed, Google search, and Cochrane library for eligible studies from 1950 until July 1 2016 published in English language. Data of 199 patients were retrieved from 94 publications for statistical analysis. Median age of the entire cohort was 49 years (range 7-91 years). The analysis revealed that a clear twofold higher incidence in male with male-to-female ratio was 2.4:1 (140:57). Mandible was found to be the commonest tumor location in 66.7% (n = 132) cases followed by maxilla (31.8%) (n = 64). The present analysis revealed that median PFS of 57 months (95% CI 39-120 months) with 5- and 10-year PFS was found to be 47.88 and 29.48%, respectively. Median OS for the entire cohort which was 122 months (95% CI 96-153 months) with 2- and 5-year OS for the entire cohort was 87.16 and 69.08%, respectively. In univariate analysis, patients with an R0 resection were found to have a favourable survival. In addition, patients with localized disease and younger age were found to have a better survival. Adjuvant radiation did not confer any survival advantage. The present analysis revealed excellent outcome for patients treated with an R0 resection. Older patients with high-risk factor may benefit from adjuvant radiation. Role of chemotherapy needs to be evaluated.

Esthesioneuroblastoma with large intracranial extension treated with Induction chemotherapy, de-bulking surgery and image guided intensity modulated radiotherapy.

INTRODUCTION: Esthesioneuroblastoma is a rare tumour of the sino-nasal tract. One-third cases present with intracranial extension. However, treatment options are limited for such cases. METHODOLOGY: We herein report a case with large intracranial extension treated with Induction chemotherapy, de-bulking surgery, and image guided intensity modulated radiotherapy. RESULTS: The patient was treated with IGIMRT technique to a dose of 64 Gy in 32 fractions. Cone bean CT verification was done twice a week to eliminate set up error. The patient achieved complete resolution of the disease and was disease free 6 months after completion of treatment. CONCLUSION: IGIMRT even after a de-bulking surgery may help to achieve long-term disease control for patients with large intracranial extension with minimal morbidity.

Microbiome and Abdominopelvic Radiotherapy Related Chronic Enteritis: A Microbiome-based Mechanistic Role of Probiotics and Antibiotics.

Chronic diarrhea and abdominal pain after radiotherapy continue to be a problem in cancer survivors. Gut microbiomes are essential for preventing intestinal inflammation, maintaining intestinal integrity, maintaining enterohepatic circulation, regulating bile acid metabolism, and absorption of nutrients, including fat-soluble vitamins. Gut microbiome dysbiosis is expected to cause inflammation, bile acid malabsorption, malnutrition, and associated symptoms. Postradiotherapy, Firmicutes and Bacteroidetes phylum are significantly decreased while Fusobacteria and other unclassified bacteria are increased. Available evidence suggests harmful bacteria Veillonella, Erysipelotrichaceae, and Ruminococcus are sensitive to Metronidazole or Ciprofloxacin. Beneficial bacteria lactobacillus and Bifidobacterium are relatively resistant to metronidazole. We hypothesize and provide an evidence-based review that short-course targeted antibiotics followed by specific probiotics may lead to alleviation of radiation enteritis.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer - Learnings From the COVID Pandemic.

INTRODUCTION: Low middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. METHODS: We conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. RESULTS: No patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). CONCLUSIONS: FAST FORWARD protocol RT in LABC appears well tolerated.

Outcomes of De Novo Oligometastatic Breast Cancer Treated With Surgery of Primary and Metastasis Directed Radiotherapy.

OBJECTIVES: With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. METHODS: Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. RESULTS: Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1 mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. CONCLUSION: Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

A Systematic Review of Clinical Trials Comparing Radiation Therapy Versus Radical Prostatectomy in Prostate Cancer.

The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel-Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.

Rosette Forming Glioneural Tumor Treated with Conformal Radiation.

Rosette forming glioneural tumors (RGNT) are a rare type of low-grade brain tumor included in 2007 in WHO classification. Given the benign nature of the disease, a complete surgical excision has been considered optimum. However, a handful of cases have reported the locally aggressive nature of RGNT. In addition, radiation may also be considered for a tumor located in areas where surgical excision is difficult. We present a similar case, where surgical risk was weighed against resection and we treated the patient with conformal radiation.

Demography, patterns of care, and survival outcomes in patients with salivary duct carcinoma: an individual patient data analysis of 857 patients.

Aim: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. The optimal treatment protocols are debated. Methodology: A systematic search and individual patient data analysis of published cases of SDC was performed. SPSS v21 was used for statistical analysis. Results: Data of 857 patients available. Median overall survival (OS) and progression-free survival (PFS) of the entire cohort 42 months and 24 months. Nodal involvement, males, primary size >5 cm, androgen receptor (AR) negativity significantly worse OS. Patients with surgery had a favorable median PFS (p = 0.000) and OS (p = 0.077). Patients with adjuvant radiation had better PFS (30 vs 18 months; p = 0.077). Conclusion: SDC has modest survival. Surgery and adjuvant radiation should be advocated for all patients. AR expression appears prognostic for survival.

Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy.

BACKGROUND: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. METHODOLOGY: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. RESULTS: An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. CONCLUSION: Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.

A Systematic Review and Meta-analysis of the Impact of Radiation-Related Lymphopenia on Outcomes in High-Grade Gliomas.

Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.