Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes.

BACKGROUND: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas ('early glioblastoma'). METHODOLOGY: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers-MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. RESULTS: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2-90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. CONCLUSION: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Systemic inflammatory biomarkers in primary central nervous system lymphoma versus high-grade glioma: exploratory, comparative and correlative analysis.

Aim: To assess systemic inflammatory biomarkers in non invasive differential diagnosis of primary central nervous system lymphoma (PCNSL) from high-grade glioma (HGG). Materials & methods: Patients with similar morphology (PCNSL or HGG) on conventional neuro-imaging were included. Systemic inflammatory indices were calculated from pretreatment complete blood counts and liver function tests and compared against histopathology as reference standard. Results: Mean values of absolute lymphocyte count and prognostic nutritional index were significantly different between PCNSL (n = 42) versus HGG (n = 16). Area under receiver operating characteristics curve for absolute lymphocyte count and prognostic nutritional index in the diagnosis of PCNSL was 0.70 and 0.72 respectively suggesting fair and acceptable diagnostic accuracy. Conclusion: Systemic inflammatory biomarkers complement established clinico-radiological features and aid in the differential diagnosis of PCNSL from HGG.

There exists a complex interplay between cancer and inflammation that can manifest as increased inflammatory biomarkers in blood. However, utility of systemic inflammatory biomarkers in the non invasive differential diagnosis of primary brain lymphoma from high-grade glioma is generally lacking. Two simple serum biomarkers, absolute lymphocyte count and prognostic nutritional index, easily derived from routine pretreatment blood tests have fair correlation and acceptable diagnostic accuracy in differentiating brain lymphoma from glioma in patients with similar morphology on MRI.

Stereotactic body radiation therapy for medically inoperable early-stage lung cancer: Tata Memorial Hospital perspective and practice recommendations.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is now considered the standard treatment for medically inoperable early-stage non-small lung cell cancer (ES-NSCLC). PURPOSE: There is a paucity of data related to outcomes with SBRT in ES-NSCLC from the developing countries. We report the early outcomes of ES-NSCLC patients treated with SBRT at our institute. MATERIALS AND METHODS: Between 2007 and 2015, 40 consecutive patients with histologically proven ES-NSCLC were treated with SBRT. Median age was 71 years (range: 46-88 years) and median Charlson comorbidity index (CCI) was 3. The majority had stage I (70%) and 45% of the tumors were centrally located. The median tumor diameter was 3.8 cm (range: 2-7.6 cm). The mean gross tumor volume was 41 cc (range: 4-139 cc) and the mean planning target volume (PTV) was 141 cc (range: 27-251 cc). Varying dose and fraction (fr) sizes were used depending on tumor location, tumor size, and treatment period. The median biologically effective dose (BED) was 77 Gy10 (range: 77-105 Gy10) for the initial cohort (2007-2012) and 105 Gy10 (range: 77-132 Gy10) for the subsequent cohort (2013-2015). RESULTS: After a median follow-up of 16 months (range: 3-99 months), the 2-year local control (LC), overall survival, and cancer-specific survival (CSS) rates were 94%, 41%, and 62%, respectively. The univariate and multivariate analysis determined CCI >3 and PTV >80.6 cc as significant predictors of worse OS and CSS (P< 0.01). The clinical stage, tumor location, BED, and treatment period (2007-2012 vs. 2013-2015) did not significantly predict any of the outcomes. The most common acute toxicities were skin erythema (10%), grade 1 esophagitis (8%), and exacerbation of previous chronic obstructive pulmonary disease (10%). Grade ≥2 late radiation pneumonitis was seen in 17.5%. One patient developed a rib fracture. No neurological or vascular complications were seen. CONCLUSIONS: SBRT results in excellent local control (LC) and acceptable survival in medically inoperable ES-NSCLC with minimal adverse effects. Charlson comorbidity index and target volume are important prognostic factors and may aid in patient selection.

Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma.

Aim: To prospectively assess the clinical utility of pretreatment flouro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with primary central nervous system (CNS) lymphoma (PCNSL). Materials & methods: Patients with suspected/proven PCNSL underwent baseline whole-body 18F-FDG-PET/CT. Maximum standardized uptake value and tumor/normal tissue ratios were compared between CNS lymphoma and other histological diagnoses. Results: The mean maximum standardized uptake value (27.5 vs 18.2; p = 0.001) and mean tumor/normal tissue ratio (2.34 vs 1.53; p < 0.001) of CNS lymphoma was significantly higher than other histologic diagnoses. Five of 50 (10%) patients with biopsy-proven CNS lymphomas had pathologically increased FDG-uptake at extraneuraxial sites uncovering systemic lymphoma. Conclusion: Pretreatment whole-body 18F-FDG-PET/CT provides valuable complementary information in the diagnostic and staging evaluation of patients with PCNSL to guide therapeutic decision-making.

Early toxicity and treatment outcomes of extended field-intensity modulated radiotherapy for cervical cancer patients with para-aortic nodal metastasis.

OBJECTIVE: Extended-field radiotherapy (EFRT) with concurrent chemotherapy represents standard treatment in cervical cancer patients with para-aortic lymph nodal (PALN) metastasis. While EFRT with Intensity Modulated RT (IMRT) has been demonstrated to reduce toxicities, the dose thresholds for minimizing acute toxicity is not clear. The present study was undertaken to report the early toxicity with extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix in our cohort of patients and determine dose-volume parameters that predict ≥grade II haematological toxicity and diarrhoea. METHODOLOGY: This was a retrospective study of consecutive cervical cancer patients with PALN metastasis treated with EF-IMRT. Patients received rotational IMRT +/- neoadjuvant chemotherapy (NACT) and/or concurrent chemotherapy (45-50 Gy/25#/5 weeks) followed by high-dose rate brachytherapy. Acute haematological and gastrointestinal toxicity (diarrhoea and vomiting) was correlated with doses received by bowel and marrow. Receiver operator characteristics curves were used for deriving thresholds that predict for increased toxicity and tested on univariate and multivariate analysis. Finally, disease free and overall survival (DFS and OS) was calculated. RESULTS: A total of 43 patients were included. One-fourth of the patients (11/43) received NACT and 88% received concurrent chemotherapy. Within the upfront EF-IMRT cohort, 22.6% and 9.7% patients developed grade ≥III haematological (HT) and gastrointestinal (GI) toxicity respectively, with an increase in HT (≥ grade III HT =67%) in patients receiving NACT (p = 0.007). In the entire cohort bone marrow Volume receiving 10 Gy (V10>) 90% correlated with an increase in ≥ grade III HT (p = 0.05). No dose volume thresholds could be validated for GI toxicity. The OS and DFS at 2 years was 56% and 54%, respectively. CONCLUSION: EF-IMRT is a feasible option for cervical cancer patients with PALN involvement and is associated with acceptable grade III toxicity. Future studies need to focus on minimizing HT toxicity.

Locally advanced cervical cancer: A study of 5-year outcomes.

BACKGROUND: Cervical cancer is the second most common cancer among Indian women. This present retrospective study was conducted to report patient outcomes with locally advanced cervical cancer treated in the year 2010. MATERIALS AND METHODS: Case records of cervical cancer patients registered from January 1, 2010, to December 31, 2010 were retrieved. A total of 1200 patients were registered, of which 583 received either definitive or adjuvant radiotherapy (RT). Of these, 345 patients who received complete treatment at our hospital were included for outcome analysis. Descriptive statistics were used to summarize patient- and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. RESULTS: The median age was 56 years (range: 33-90). Squamous carcinoma was the most common histology (91.4%) and the majority were FIGO Stage III (45.4%). Median follow-up of the cohort was 44 months (1-85 months). The 5-year disease-free survival (DFS) across stages was 50%. Most important predictor of DFS was FIGO staging (Stage II vs. Stage III: 62% vs. 45%) and use of concurrent chemoradiotherapy (CTRT) l (RT vs. CTRT: 32% vs. 57%, respectively). Patients aged >70 years had a significantly poor DFS at 5 years; however, did not have any effect on survival. Grade 3 or more late toxicity was seen in only 5% of the patients. CONCLUSION: Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.

Effect of imaging frequency on PTV margins and geographical miss during image guided radiation therapy for prostate cancer.

BACKGROUND: The relationship between frequency of imaging during image guided radiation therapy (IGRT) and planning target volume (PTV) margin remains unclear. This issue is of practical significance given resource and time intensive nature of IGRT. The purpose of this study was to evaluate PTV margins with predefined and commonly used less-than-daily IGRT schedules using data obtained from patients treated with daily IGRT for prostate cancer. METHODS AND MATERIALS: Daily setup error and 3-dimensional daily alignment data for a total of 108 consecutive patients with prostate cancer treated with 2700 fractions of daily image guidance on tomotherapy were retrospectively analyzed. Five IGRT scenarios were simulated: alternate day, twice weekly, once weekly, first 3 days only, and no image guidance. The daily alignment data were modeled to simulate the 5 predefined scenarios by applying appropriate corrections to determine the PTV margin for each image guidance scenario. The data were also analyzed to predict possible geographical miss in any direction using 2 frequently used PTV margins of 7 and 5 mm for all the scenarios. RESULTS: Decreasing the frequency of image guidance increased the mean systematic error and the standard deviation of the systematic error. With decreased image guidance frequency, an increase in PTV margins was required to achieve adequate coverage of the clinical target volume. With reduction in image guidance from 50% to 12%, a gradual increase in percentage of fractions with predicted geographical miss using an isotropic PTV margin of 7 or 5 mm was seen. With every 15% decrease in imaging, a 5% increased risk of geographical miss was estimated. CONCLUSIONS: The use of less-than-daily IGRT requires larger PTV margins for patients treated with intensity modulated radiation therapy for prostate cancer. With every 15% reduction, a 5% increased risk of geographical miss was estimated.

Intraoperative radiotherapy: review of techniques and results.

Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community. Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise. IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers). This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.