Prognostic impact of semantic MRI features on survival outcomes in molecularly subtyped medulloblastoma.

PURPOSE: Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report on the prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. METHODS: Sixteen semantic imaging features (with predefined categories) were extracted from pre- and postcontrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess the correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). RESULTS: The study cohort comprised 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths, including one treatment-related death. At a median follow-up of 45 months (interquartile range 19-65 months), 5­year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast uptake, heterogenous pattern of contrast enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS in univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. CONCLUSION: Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma, also within individual molecular subgroups, reflecting their prognostic impact.

Impact of immobilisation and image guidance protocol on planning target volume margins for supine craniospinal irradiation.

Background: The setup errors during supine-CSI (sCSI) using single or dual immobilisation (SM, DM) subsets from two institutions were reviewed to determine if DM consistently decreased the required planning target volumes (PTV) margins and to identify the optimal image guidance environments. Materials and methods: Ours and a sister institutional cohort, each with a subset of SM or DM sCSI and daily 3-dimensional online image verification sets, were reviewed for the cranial and spinal regions translational shifts. Using descriptive statistics, scatter plots and independent sample Mann-Whitney test we compared shifts in each direction for two subsets in each cohort deriving PTV margins (Van Herk: VH, Strooms: St recipes) for the cranial and spinal regions. Three image guidance (IG) protocols were simulated for two regions on the combined cohort with SM and DM subsets to identify the most optimal option with the smallest PTV margin. The IG protocols: 3F, 5F and 5FB where the systematic error correction was done using the average error from the first three, five and in the cranium alone (applied to both the cranium and spine, otherwise) for the first five set-ups, respectively. Results: 6968 image sets for 179 patients showed DM could consistently reduce the PTV margin (VH/St) for the cranium from 6/5 to 4/3.5 (31.8/30.8%) and 6/4 to 4/3.5 mm (30.5/16.8%) for primary and validation cohort, respectively. Similarly, for the spine it was 10/8.5 to 6/5.5 (38.6/38.4%) and 9/7.7 to 7/6 (21.6/21.4%), respectively. The "5F-IG" resulted in the smallest margins for both the cranial (3 mm) and spinal region (5 mm) for DM with estimated 95% CTV coverage probability. Conclusion: DM with 5F-IG would significantly reduce the required PTV margins for sCSI.

Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting.

PURPOSE: To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm2 or leptomeningeal metastases. METHODS: This single-arm combined prospective (2005-2011) and retrospective (2011-2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high-risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m2 ) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy. RESULTS: All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment-related toxicity. Grade 3-4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony-stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment-related deaths during the concurrent chemo-radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications. At a median follow-up of 82 months, the 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival. CONCLUSION: Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high-risk/metastatic medulloblastoma.

Clinical approach to re-irradiation for recurrent diffuse intrinsic pontine glioma.

BACKGROUND: We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes. METHODS: Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015-September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan-Meier method and log-rank test were used for survival analysis. RESULTS: Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6-41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage. CONCLUSIONS: Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.

Cabergoline may act as a radioprotective agent in Cushing's disease.

CONTEXT: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. OBJECTIVE: To determine long-term outcome of CRT and its predictors in CD patients. DESIGN, SETTING AND PATIENTS: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. RESULTS: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). CONCLUSION: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.

Extent of re-excision, sequence/timing of salvage re-irradiation, and disease-free interval impact upon clinical outcomes in recurrent/progressive ependymoma.

PURPOSE: To report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma. METHODS: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive ependymoma were analyzed retrospectively. The linear-quadratic model was used to provide estimates of biologically effective dose (BED) of irradiation using an α/ß value of 2 for late CNS toxicity for each course of irradiation and summated to derive cumulative BED without correcting for the assumed recovery. RESULTS: A total of 55 patients (median age 10 years at index diagnosis) treated with curative-intent re-RT between 2010 and 2018 were included. Median time to first recurrence was 29 months with an inter-quartile range (IQR) of 16-64 months. Majority (n = 46, 84%) of patients underwent surgical re-excision of recurrent disease. Median interval from first course of irradiation (RT1) to second course (RT2) was 35 months (IQR = 26-66 months) with a median re-RT dose of 54 Gy in 30 fractions (range 40-60 Gy), resulting in median cumulative equivalent dose in 2 Gy fraction (EQD2) of 106.2 Gy (range 92.4-117.6 Gy). Volume of re-RT was based on location and pattern of relapse, comprising uni-focal (n = 49, 89%), multi-focal (n = 3, 5.5%), or craniospinal irradiation (CSI) in 3 (5.5%) patients respectively. Thirty-six (66%) patients received platinum-based salvage chemotherapy either before or after RT2. At a median follow up of 37 months (range 6-80 months), the Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) for the entire study cohort were 40% and 51% respectively. Gross total resection at recurrence; early salvage re-RT (prior to chemotherapy, if any); and longer (> 2 years) disease-free interval (DFI) were associated with better survival outcomes. Salvage re-RT was generally well tolerated with only 3 (5.5%) patients developing symptomatic radiation necrosis necessitating corticosteroids. CONCLUSION: Extent of re-excision, sequence/timing of re-RT, and DFI impact upon outcomes in curative-intent, multi-modality salvage therapy for recurrent ependymoma.

Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping.

PURPOSE: To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB). METHODS: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively. RESULTS: A total of 28 patients (median age 18 years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4 MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5 months (range 24-98 months) with median cumulative biologically effective dose of 117 Gy (range 78-132 Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24 months (range 6-84 months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18 years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes. CONCLUSION: Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.

Pediatric Patients With SHH Medulloblastoma Fail Differently as Compared With Adults: Possible Implications for Treatment Modifications.

PURPOSE: The purpose of this work was to study the diversity of sonic hedgehog (SHH) medulloblastoma across different age groups with an emphasis on patterns of relapse. METHODS: All data for the study were obtained through review of medical records, imaging, radiation charts, treatment planning, and chemotherapy details. RESULTS: Sixty-three patients with SHH medulloblastoma were identified from a prospectively maintained database and classified into 3 groups-infantile: ≤3 years (i-SHH, n=11); pediatric: >3 to <18 years (p-SHH, n=21); and adult: ≥18 years (a-SHH; n=31). Lateralized tumors were common with increasing age (81% a-SHH, 67% p-SHH, 27% i-SHH; P=0.01). Large cell anaplastic histology was relatively common for p-SHH (33%), while the nodular/desmoplastic variant was more frequent in i-SHH (64%) and adults (51%). Median follow-up was 38 months (range, 5 to 91 mo). Five-year event-free survival was 80%, 31%, and 52% for i-SHH, p-SHH, and a-SHH, respectively (P=0.001). Median time to failure for p-SHH and a-SHH were 12 and 36 months, respectively. For p-SHH, 83% were metastatic relapses compared with localized failure in 75% for a-SHH. Five-year overall survival for i-SHH, p-SHH, and a-SHH were 91%, 31%, and 70%, respectively (P=0.001). On univariate analysis, event-free survival was significantly worse for superiorly located tumors (P=0.01), nondesmoplastic histology (P=0.02), and histology alone for overall survival (P=0.04) (none on multivariate analysis). CONCLUSIONS: SHH medulloblastoma demonstrates varied outcomes depending on age, with p-SHH associated with early and metastatic relapses, while for a-SHH it tends to be delayed and localized.

Distinct demographic profile and molecular markers of primary CNS tumor in 1873 adolescent and young adult patient population.

INTRODUCTION: We present detailed demographic profile, tumor types, and their molecular markers in adolescent and young adult (AYA) patients of age group between 15 and 39 years with primary central nervous system (PCNS) tumors, and compare with pediatric and adult patient populations. METHODOLOGY: Demographic- and disease-related information of 1873 PCNS tumor patients of age 15-39 years registered between 1 January 2011 and 31 December 2015 at our institution was analyzed with respect to their demographics and tumor subtypes. Various molecular markers for glial tumors and subgroup classification of medulloblastoma were evaluated for AYA, pediatric, and older adult patient populations. RESULTS: AYA constituted 27% of all PCNS. Median age was 29 years. Glial tumors (62.36%) comprised the largest tumor type with astrocytoma (38.55%) being the most common histology. Glioblastoma (51.52%) was the commonest astrocytic tumor with 74.67% of them being isocitrate dehydrogenase 1 (IDH1) negative and 41.38% with O (6)-methylguanine DNA methyltransferase (MGMT) promoter methylated. Diffuse astrocytoma and glioblastoma showed significantly higher IDH1 positivity and loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) for AYAs as compared to pediatric and adult patient populations (p < 0.0001). Medulloblastoma (73.8%) was the most commonly diagnosed embryonal tumor, with sonic hedgehog (SHH) being the commonest molecular subtype (48%). Younger patients among AYA population presents with pediatric type of tumor spectrum, while older ones present with more aggressive tumor subtypes. CONCLUSION: This is among the few studies reporting spectrum of PCNS tumor in AYA population with distinct tumor subtypes and molecular profiles. AYA patient populations may need special attention with appropriately designed clinical trials.

Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: A population-based study.

BACKGROUND: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METHODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes. CONCLUSIONS: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND METHODS: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Translation and pilot validation of Hindi, Marathi, and Bangla translation of quality of life EORTC module (QLQ-SH-22) for assessing sexual health-related quality of life.

AIM: To translate and validate the European Organization for Research and Treatment for Cancer (EORTC) module for assessing the sexual health-related quality of life in cancer patients (QLQ-SH22), in Hindi, Marathi, and Bangla languages for clinical use. METHODS AND RESULTS: The EORTC QLQ-SH-22 was translated into Hindi, Marathi, and Bangla by adopting standard guidelines given by EORTC. Initially, the original questionnaire was forward translated by two separate translators, followed by the reconciliation of the forward translations by a third person. This was followed by two back translations of the reconciled version into English by two other translators. These back-translated questions were then compared with the original EORTC questions for accuracy, and once acceptable, a preliminary questionnaire was prepared in all three languages. These questionnaires were then pilot tested with 30 patients (10 for each language) diagnosed with any of the cancers in the pelvic region who are expected to be at risk of sexual quality of life due to tumor or treatment like pelvic radiotherapy. Participated patients had never seen or filled the questionnaire before, each patient was interviewed after filling the questionnaire for difficulty in answering, confusion, difficulty understanding, or if any of the questions were upsetting and if patients would have asked the question differently. RESULTS: None of the patients reported any changes or suggestions for all the three translations. All the translated questionnaires were well understood by all the patients. Pilot testing reports were sent to EORTC. After reviewing the entire report of Hindi, Marathi, and Bangla translations, these questionnaires were approved by the EORTC translation unit. The questionnaires are reliable with Cronbach's α for Hindi, Marathi, and Bangla being 0.69, 0.66, and 0.86, respectively. CONCLUSION: The final Hindi, Marathi, and Bangla translations of SH 22 have been approved by the EORTC and can be used to assess the sexual health of cancer patients in routine oncology practices and/or clinical studies.

Translation and Pilot Validation of Hindi, Marathi, and Bangla Translation of Quality-of-Life EORTC Radiation Proctitis Module (PRT-20) for Routine Clinical Use.

Rahul Krishnatry The aim of this study was to translate and validate the European Organization for Research and Treatment for Cancer (EORTC) "Radiation Proctitis" (PRT-20) module in Hindi, Marathi, and Bangla languages. The EORTC PRT-20 was translated into Hindi, Marathi, and Bangla using EORTC guidelines. Two separate translators first translated the original questionnaire into the three regional languages, following which a reconciled forward translation was compiled. This reconciled version in each language was then back-translated into English by two other translators. This back-translated version was then compared with the original the EORTC questionnaire for correctness, and the preliminary questionnaires were formed in all three languages. The EORTC translation unit approved the questionnaires. The preliminary questionnaires were administered to 30 patients (10 for each language) diagnosed with rectal or anal canal cancer who had received pelvic radiotherapy and were at risk of developing PRT. None of the patients had seen the questionnaire before. After filling out the questionnaire, each patient was interviewed for difficulty in answering, confusion, understanding, or if any of the questions were upsetting and if patients would have asked the question differently. No changes were suggested for Marathi and Bangla translations. Two modifications were suggested in the Hindi translation, which was then retested in five patients and finalized. All the suggestions were incorporated into the preliminary questionnaires, which were sent back to the EORTC for final approval. After reviewing the entire report of pilot testing for the translated quality-of-life questionaire-PRT-20 in three languages, it was approved by the EORTC translation unit. The translated questionnaires were reliable, with Cronbach α values of 0.767, 0.799, and 0.898 for Hindi, Marathi, and Bangla, respectively. The Hindi, Marathi, and Bangla translations of PRT-20 have been approved by the EORTC and can be used in routine clinical practice.

Tata Memorial Centre Evidence Based Management of Colorectal cancer.

ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.

Evaluation of interobserver and interscale agreement in assessing late bowel toxicity after pelvic radiation in patients with carcinoma of the cervix.

BACKGROUND: Lack of agreement and inconsistency in capturing late bowel toxicity may be a source of error while reporting trials with toxicity endpoints. Documenting baseline inconsistency while scoring toxicity questionnaires (RTOG/EORTC and CTCAE) may be worthwhile. The present study was conducted as a quality assurance measure prior to initiating a randomized trial (PARCER; NCT01279135) that evaluates the impact of image-guided radiation on bowel toxicity. METHODS: From August 2010 to July 2011, patients with cervical cancer who underwent pelvic chemoradiation >6 months ago, with controlled disease and any bowel symptom at follow-up, were included. RTOG and CTCAE questionnaires were filled by two blinded observers. Interscale (RTOG vs CTCAE) and interobserver (observer A and B) agreement were evaluated with Spearman's correlation and kappa statistic. RESULTS: Fifty-five patients were included. Twelve patients with symptoms could not be graded by the RTOG scale. Of those graded as asymptomatic on RTOG, distension, vomiting, pain and nausea were identified as the most common symptoms. Amongst these, grade 1, 2 and 3 toxicity was observed in 6, 5 and 1 patient, respectively. The interscale correlation was moderate (Spearman's correlation ρ = 0.56; P = 0.001). High interobserver agreement (92%) was observed within the RTOG scale [kappa (κ) -0.94; 95% CI 0.77-1]. All disagreements were observed while scoring grade 1-2 toxicity. Among CTCAE, agreement was lower with modules such as distension, anorexia, nausea and constipation. CONCLUSIONS: High interobserver agreement was observed for both RTOG and most CTCAE subscales; most disagreements were for grade 1-2. Interscale agreement (RTOG and CTCAE) was moderate. Detailed patient interrogation or use of patient-reported-outcome scores while documenting the aforesaid subscales may be worthwhile.

Institutional Patterns of Care of Diffuse Intrinsic Pontine Glioma.

Background and Aim: Despite recent advances, the outcomes of diffuse intrinsic pontine glioma (DIPG) remain dismal. This is a retrospective study to understand the pattern of care and its impact on DIPG patients diagnosed over 5 years in a single institute. Subjects and Methods: DIPGs diagnosed between 2015 and 2019 were retrospectively reviewed to understand the demographics, clinical features, patterns of care, and outcomes. The usage of steroids and response to treatment were analyzed as per the available records and criteria. The re-irradiation cohort was propensity matched with patients with a progression-free survival (PFS) >6 months treated with supportive care alone based on PFS and age as a continuous variable. Survival analysis was performed using the Kaplan-Meier method, and Cox regression model was used to identify any potential prognostic factors. Results: One hundred and eighty-four patients were identified with demographic profiles similar to western population-based data in the literature. Of them, 42.4% were residents from outside the state of the institution. About 75.2% of patients completed their first radiotherapy treatment, of which only 5% and 6% had worsening clinical symptoms and persistent need for steroids 1 month posttreatment. On multivariate analysis, Lansky performance status <60 (P = 0.028) and cranial nerve IX and X (P = 0.026) involvement were associated with poor survival outcomes while receiving radiotherapy with better survival (P < 0.001). In the cohort of patients receiving radiotherapy, only re-irradiation (reRT) was associated with improved survival (P = 0.002). Conclusion: Many patient families still do not choose radiotherapy treatment, although it has a consistent and significant positive association with survival and steroid usage. reRT further improves outcomes in the selective cohorts. Involvement of cranial nerves IX and X needs improved care.

Optimizing Target Volume for Adjuvant Radiation Therapy in Penile Cancer.

PURPOSE: Recent studies have reported improved outcomes with adjuvant radiation therapy in penile cancer. However, the appropriate target volumes to be irradiated in this group of patients for optimal outcomes are still unclear. This study aims to report the patterns of failure and define target volumes to be irradiated in patients with pN3 penile cancer. METHODS AND MATERIALS: Patients with pT1-T4, pN3, cM0, and squamous cell carcinoma of the penis who received adjuvant radiation therapy (involved field or extended field), with or without concurrent chemotherapy were included in the study. Complete information on disease characteristics, radiation therapy target details, and patterns of failure were available for 75 patients. Disease-free (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and log-rank test was used to compare survival outcomes between the involved field and extended field radiation therapy groups. Multivariate analysis was performed using the Cox proportional hazards model to analyze factors correlating with survival outcomes. RESULTS: At a median follow-up of 39 months, 38.6% (29/75) of patients had relapsed either locally, regionally, or at distant sites. Of the 24 patients who received extended field radiation therapy (EFRT), only 1 (4%) patient experienced relapse. Twenty-eight (55%) patients experienced relapse after involved-field radiation therapy (IFRT), of which 28.5% were regional-only relapses and 64% relapses were associated with a regional component. The 2-year DFS and OS of the entire cohort were 62.2% and 70.8%, respectively. The 2-year DFS was 67.9% in patients who received IFRT and 94.1% in those who received EFRT (P = .002), and the 2-year OS was 62.4% with IFRT and 91.1% with EFRT (P = .014). Extended field radiation therapy was associated with an improved DFS (hazard ratio, 12.2; 95% confidence interval, 1.5-97.4; P = .02) and OS (hazard ratio, 4.6; 95% confidence interval, 1-21.5; P = .05) on multivariate analysis. CONCLUSIONS: Extended field radiation therapy significantly improves clinical outcomes compared with involved-field radiation in patients with pN3 penile cancer.

Utilising alternative cystoscopic schedules to minimise cost and patient burden after trimodality therapy for muscle-invasive bladder cancer.

BACKGROUND: To assess urinary symptoms and urine cytology as screening tools for cystoscopic detection of local recurrence after bladder-preserving trimodality treatment (TMT). METHODS: Patients with muscle-invasive bladder cancer receiving definitive TMT follow-up three monthly for 2 years, six monthly for the next 3 years and then yearly, with a clinical review, urine cytology and cystoscopy at each visit (triple assessment, TA). Grade 2+ cystitis/haematuria absent/present was scored 0/1, and urine cytology reported negative/suspicious or positive was scored 0/1, respectively. The performance of these two parameters for predicting local recurrence in cystoscopic biopsy was tested. Other hypothetical surveillance schedules included cystoscopy on alternate visits (COAV), or suspected recurrence (COSR), six-monthly COSR and six-monthly TA. RESULTS: A total of 630 follow-up visits in 112 patients with 19 recurrences (7 muscle invasive, 12 non-muscle invasive) at a median follow-up of 19 months were analysed. The sensitivity and specificity of clinical symptoms were 47.4% and 92%, and for urine cytology 58% and 85%, respectively. The combination of clinical symptoms and cytology (COSR) was 95% sensitive and 78% specific for local recurrence but 100% sensitive for muscle-invasive recurrence. Both COAV and COSV schedules showed a high area under the curve (AUC) for detecting local recurrence (COAV = 0.84, COSR = 0.83), muscle-invasive recurrence (AUC = 0.848 each) and non-muscle-invasive recurrence (COAV = 0.82, COSR = 0.81); reducing the need for TAs by 64% and 67% respectively, and overall cost by 18% and 33%, respectively. CONCLUSION: Cystoscopy at suspected recurrence during follow-up is safe and the most cost-effective for detecting muscle-invasive local recurrences, while cystoscopy at alternate visits may be more optimal for detecting any local recurrence.

Management of testicular tumours in patients with undescended testes- a challenging but rewarding task: experience from a tertiary care cancer centre in India.

Objective: Primary objective: To study patients' clinical profile and outcomes with germ cell tumours developing in undescended testes. Materials and methods: Case records of patients enlisted in the prospectively maintained 'testicular cancer database' at our tertiary cancer care hospital from 2014 to 2019 were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with a documented history/diagnosis of undescended testes, whether surgically corrected or not, was considered for this study. The patients were managed along the standard lines of treatment for testicular cancer. We evaluated clinical features, difficulties and delays in diagnosis and complexities in management. We evaluated event-free survival (EFS) and overall survival (OS) using the Kaplan-Meier Method. Results: Fifty-four patients were identified from our database. The mean age was 32.4 years (median age 32, range: 15-56 years). Seventeen (31.4%) had developed cancer in orchidopexy testes, and 37 (68.6%) presented with testicular cancer in uncorrected cryptorchid testes. The median age at orchidopexy was 13.5 years (range: 2-32 years). The median time from symptom onset to diagnosis was 2 months (1-36 months). There was a delay in the initiation of treatment of more than 1 month in 13 patients, with the longest delay being 4 months. Two patients were initially misdiagnosed as gastrointestinal tumours. Thirty-two (59.25%) patients had seminoma, and 22 (40.7%) patients had non-seminomatous germ cell tumours (NSGCT). Nineteen patients had metastatic disease at presentation. Thirty (55.5%) patients underwent orchidectomy upfront while in 22 (40.7%) patients, orchidectomy was done after chemotherapy. The surgical approach included high inguinal orchidectomy, exploratory laparotomy or laparoscopic surgery per the clinical situation. Post-operative chemotherapy was offered as clinically indicated. At a median follow-up of 66 months (95% CI: 51-76), there were four relapses (all NSGCT) and one death. The 5-year EFS was 90.7% (95% CI: 82.9-98.7). The 5-year OS was 96.3% (95% CI: 91.2-100). Conclusions: The tumours in undescended testes, particularly those without prior orchiopexy, often presented late and with bulky masses, requiring complex multidisciplinary management. Despite the complexity and challenges, our patient's OS and EFS matched that of patients with tumours in normally descended testes. Orchiopexy may help in earlier detection. In the first such series from India, we show that testicular tumours in the cryptorchid are also as curable as the germ cell tumours developing in the descended testis.A multidisciplinary disease management group with expertise in managing complex cases is crucial for a favourable outcome in these groups of patients. We also found that orchiopexy done even later in life confers an advantage in terms of early detection in a subsequently developing testicular tumour.

CT or MRI for image-based brachytherapy in cervical cancer.

OBJECTIVE: To compare volumes and doses of tumour and organs at risk with computed tomography vs. magnetic resonance imaging in cervical cancer brachytherapy. METHODS: Seventeen previously untreated patients with cervical cancer suitable for radical treatment were included. All patients underwent brachytherapy using a magnetic resonance imaging-compatible applicator followed by both computed tomography and magnetic resonance imaging. The tumour and organs at risk (bladder, rectum, sigmoid and intestines) were contoured on computed tomography using only clinical findings and on magnetic resonance imaging using GEC-ESTRO guidelines. The volume and doses for tumour and organs at risk were evaluated using two-sided t-test. RESULTS: When magnetic resonance imaging information is not included in contouring on computed tomography images, there is significant underestimation of tumour height and overestimation of the width (P< 0.05). However, there was no significant difference in V(100), D(90) and D(100) for high- and intermediate-risk clinical target volume in computed tomography and magnetic resonance imaging. The volumes and doses to 0.1, 1 and 2 cc for organs at risk were also similar. CONCLUSIONS: Magnetic resonance imaging remains the gold standard for tumour delineation, but computed tomography with clinical information can give comparable results, which need to be studied further. Computed tomography-based contouring can be used comfortably for delineation of organs at risk.