Late toxicity within a Phase III clinical trial of IG-IMRT in cervix cancer (PARCER): Reanalysis with time weighted adverse event reporting (MOSES).

BACKGROUND AND PURPOSE: This post-hoc analysis was performed to report the impact of Image guided intensity modulated radiotherapy (IG-IMRT) and three-dimensional conformal radiotherapy (3D-CRT) across organ system and grades of toxicity within PARCER trial (NCT01279135). Primary endpoint of PARCER focused on grade ≥ 2 late gastrointestinal (GI) toxicity using Common Terminology Criteria for Adverse Events (CTCAE). We now analyze all adverse events using CTCAE and time and severity weighted toxicity reporting method (MOSES). MATERIALS AND METHODS: MOSES was calculated separately for GI, genitourinary (GU)/GI, and any late toxicities (GI, GU, lymphedema, fatigue, vaginal stenosis, fibrosis and constitutional symptoms) by imputing proportionate time weightage to CTCAE. Cumulative MOSES (C-MOSES) for multiple system and multiorgan toxicity was determined. Difference in arms was analyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥ 1 and C-MOSES ≥ 0.70. RESULTS: We observed no difference in the 3-year cumulative incidence of CTCAE grade ≥ 1 GI, GI or GU, or any late toxicity between treatment arms. However, while using C-MOSES, HR of 0.59 (95% CI 0.38-0.92, p = 0.017), 0.68 (95% CI: 0.44-1.05, p = 0.08) and 0.72 (95% CI: 0.52-0.99, p = 0.04) was observed for GI, GI or GU, or any late toxicity within IG-IMRT respectively. CONCLUSION: This demonstrates superior discrimination of intervention effects using MOSES which demonstrates superiority of IG-IMRT.

Indian Brachytherapy Society Guidelines for radiotherapeutic management of cervical cancer with special emphasis on high-dose-rate brachytherapy.

Brachytherapy (BT) for locally advanced cervical cancer is vital for optimal outcomes. There is heterogeneity in brachytherapy treatment practice for cervical cancer across India. In an attempt to standardize various processes involved in cervical cancer brachytherapy, the expert members of the Indian Brachytherapy Society (IBS) developed a document related to radiation therapy treatment of cervical cancer with special emphasis on brachytherapy. The guidelines are based on high quality clinical evidence, expert opinion and consensus wherever evidence was lacking. The document provides a guide for external beam radiation and details of all the processes involved in high-dose-rate (HDR) brachytherapy including patient selection, preparation, principles and technique of BT applications, target and normal tissue definition, dose prescriptions, BT planning, reporting parameters, common complications of BT and their management, scope for research, etc. In summary, we present here practical tips and tricks, recording and reporting of cervical cancer brachytherapy, which can be implemented in various clinical environments and forms the basis of this report.

Dose escalated concurrent chemo-radiation in borderline resectable and locally advanced pancreatic cancers with tomotherapy based intensity modulated radiotherapy: a phase II study.

BACKGROUND: We report the response and outcomes of borderline resectable and locally advanced pancreatic cancer (BRPC & LAPC) patients treated with dose escalated neoadjuvant intensity modulated radiotherapy (IMRT). METHODS: Thirty newly diagnosed patients with BRPC (n=18) and LAPC (n=12) (NCCN criteria V 2.2.12) were accrued in this prospective study from 2008-2011. All patients received neoadjuvant chemoradiation (NACRT) using Helical Tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor volume (GTV) and 45 Gy over 25 fractions to suspected microscopic extension) along with weekly gemcitabine. RESULTS: Fifteen patients (50%) had a partial response. A complete metabolic response (CMR) on PET was seen in 9 patients (30%). Among BRPC, 9 patients (50%) were surgically explored and 7 underwent R0 resection (39%). The median follow up of surviving patients was 85 [interquartile range (IQR): 64.5-85.8] months. The median progression free survival (PFS) was 13 months for BRPC and 8.8 months for LAPC. The median overall survival (OS) was 17.3 months for BRPC and 11.8 months for LAPC. Among patients undergoing R0 resection, the median PFS and OS was 27 and 35.5 months respectively. CONCLUSIONS: Dose escalated radiotherapy with concurrent chemotherapy is feasible and can downsize some tumors resulting in surgery in about 39% of the BRPC.

Cancer cervix: Establishing an evidence-based strategy, an experience of a tertiary care centre in India.

Carcinoma cervix is a common cancer among Indian women. Evidence based management is essential for best practice in treatment of carcinoma cervix for its effective control. The current imaging system like CT, MRI and PET CT scans have contributed in identifying the patients for optimal treatment and delivering treatment accurately. For stages IB2 to IV, concurrent chemoradiation is advocated with improvement in overall survival proven with randomized trials. Brachytherapy is an integral part in the radiation treatment. Imaged-guided brachytherapy using MRI is desirable, however less expensive imaging modalities such as CT and ultrasonography has been evaluated. In special situation such as for HIV positive patients and patients with neuroendocrine tumors have role of radiotherapy. For further improvement in control of cancer, it is required to integrate basic research to answer clinically relevant questions.

Gastrointestinal cancers in India: Treatment perspective.

GI cancer is not one cancer but is a term for the group of cancers that affect the digestive system including gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), esophageal cancer (EC), and pancreatic cancer (PC). Overall, the GI cancers are responsible for more cancers and more deaths from cancer than any other organ. 5 year survival of these cancers remains low compared to western world. Unlike the rest of the world where organ based specialities hepatobiliary, pancreatic, colorectal and esophagogastric exist, these cancers are managed in India by either a gastrointestinal surgeons, surgical oncologist, or a general surgeon with varying outcomes. The aim of this review was to collate data on GI cancers in indian continent. In colorectal cancers, data from tertiary care centres identifies the unique problem of mucinous and signet colorectal cancer. Results of rectal cancer resection in terms of technique (intersphincteric resection, extralevator aper, minimal invasive approach) to be comparable with world literature. However long term outcome and data regarding colon cancers and nationally is needed. Gastric cancer at presentation are advanced and in surgically resected patients, there is need for a trial to compare chemoradiation vs chemotherapy alone to prevent loco regional recurrence. Data on minimal invasive gastric cancer surgery may be sparse for the same reason. Theree is a lot of data on surgical techniques and perioperatve outcomes in pancreatic cancer. There is a high volume of locally advanced gallbladder cancers with efforts on to decide whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is better for down staging. Considering GI cancers, a heterogeneous disease with site specific treatment options and variable outcomes, the overall data and outcomes are extremely variable. Young patients with pathology unique to the Indian subcontinent (for example, signet ring rectal cancer, GBCs) need focussed attention. Solution for such pathology needs to come from the Indian continent itself. Joint efforts to improve outcomes for GI cancer can be integrated under the national cancer grid program.

Quality assurance and commissioning of an infrared marker-based patient positioning system for frameless extracranial stereotactic radiotherapy.

Rapid advancements in imaging technology have led to remarkable improvements in identification and localization of tumors, ushering the era of high-precision techniques in contemporary radiotherapy practice. However, uncertainties in patient set-up and organ motion during a course of fractionated radiotherapy can compromise precision of radiation therapy. Excellent accuracy has been achieved with invasive and non-invasive fixation systems for stereotactic radiotherapy. This report describes the commissioning procedure and Quality Assurance studies done to evaluate the accuracy of isocenter localization by an infrared marker-based positioning system (ExacTrac). The ExacTrac has two infrared cameras that emit and detect infrared rays from reflective markers and construct three-dimensional coordinates of each marker. It detects the difference of the actual isocenter position from the planned isocenter coordinates in three translational (lateral, longitudinal, vertical, or x,y,z axes) and three rotational axes (six degree of freedom). This study performed on a flat and static phantom shows excellent accuracy achieved by the ExacTrac system. The positioning accuracy of ExacTrac (± 1 mm translational displacement and ± 1° rotational errors) can be a valuable tool in implementing frameless extracranial stereotactic radiotherapy. Nevertheless, it needs to be further evaluated on patients with inherent motion and greater positional uncertainty before being adopted in clinical practice.