Pramod Kumar Julka

Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

PURPOSE To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). METHODS AND MATERIALS Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m(2). Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. RESULTS Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). CONCLUSION WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral Talactoferrin in Combination with Carboplatin and Paclitaxel in Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Cancer

Introduction: The aim of the study is to investigate the activity and safety of oral talactoferrin (TLF) plus carboplatin and paclitaxel (C/P) in patients with previously untreated stage IIIB/IV non-small cell lung cancer. Methods: Patients (n = 110) were randomly assigned to receive C/P plus either TLF (C/P/T) or placebo (C/P/P). The primary objective of this exploratory study was assessment of confirmed response rate (RR) in the prospectively defined evaluable population with a one-tailed p = 0.05. Secondary objectives included assessment of progression-free survival (PFS), duration of response, overall survival (OS), and safety. Results: The trial met the primary end point of improvement in confirmed RR in the prospectively defined evaluable population. Compared with the C/P/P group, RR increased in the C/P/T group by 18% (29–47%; p = 0.05) and 15% (27–42%; p = 0.08) in the evaluable and intent-to-treat populations, respectively. Compared with the C/P/P group, the C/P/T group had a longer median PFS (4.2 versus 7.0 months), OS (8.5 versus 10.4 months), and duration of response (5.5 versus 7.6 months), although the differences were not statistically significant. Adverse events (AEs) were consistent with C/P therapy. There were fewer total AEs (472 versus 569; two-tailed p = 0.003) and grade 3/4 AEs (78 versus 105; p = 0.05) in the C/P/T group compared with the C/P/P group. Conclusion: TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity. These results need to be confirmed in a phase III trial.

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. MATERIALS AND METHODS In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability. RESULTS Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p=0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p=0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. CONCLUSION Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

Comparison of computed tomography and magnetic resonance based target volume in brain tumors

PURPOSE This study was mainly framed to study the difference in tumor volumes as seen on computed tomography (CT) and magnetic resonance (MR) and their significance in planning. MATERIALS AND METHODS Twenty-five patients with brain tumor of different diagnoses who underwent stereotactic radiotherapy were included in this study. CT and MR imaging was done for all the patients with 2.5 mm slice thickness. The CT tumor volume and MR tumor volume were measured and compared with each other. The center of mass (CM) of the tumor volume delineated on CT and MR were computed and the shift between the two CMs was determined. RESULTS The mean and median volume of the tumor as measured from MR scans was 19.67 cc +/- 13.73 and 16.13 cc (range: 3.25 cc-50.37 cc). Similarly, the mean and median volume of the tumor as measured from CT scans was 15.05 cc +/- 10.13 and 11.63 cc (range: 3.0 cc-36.25 cc) respectively. The mean and median CM shift between CT and MR was 5.47 mm and 5.21 mm respectively. CONCLUSION The study demonstrates that MR is an indispensable imaging modality in radiotherapy for planning brain tumors.

F-18 FDG PET-CT in patients with recurrent glioma: Comparison with contrast enhanced MRI

PURPOSE The purpose of the study was to compare the efficacies of FDG PET-CT and contrast enhanced MRI in detection of recurrent gliomas. METHODS Ninety histopathologically proven glioma patients with clinical suspicion of recurrence were evaluated. All patients underwent FDG PET-CT scan and contrast enhanced MRI. Combination of clinical follow up, repeat imaging and biopsy (when available) was taken as gold standard. RESULTS Based on gold standard criteria, 59 patients were positive and 31 patients were negative for recurrence. Overall sensitivity and specificity of FDG PET-CT were 70% and 97% respectively whereas that for contrast enhanced MRI was 95% and 23%. FDG PET-CT also has higher accuracy (80%) as compared to MRI (70%). FGD PET-CT has lower sensitivity than MRI in all grades, except for Grade II gliomas where their sensitivities are comparable (95% and 90%). Very low specificity of MRI was observed in all grades of tumour (18-33%). In contrast the specificity of FDG PET-CT was high across all grades (83-100%). CONCLUSION FDG PET-CT is a highly specific modality for detecting recurrence in patients with gliomas and can effectively exclude post therapy changes.

Factors influencing early complications following Gamma Knife radiosurgery. A prospective study.

Purpose: The factors influencing early complications following Gamma Knife radiosurgery have not been definitely established. We report a prospective study evaluating the incidence of early complications (occurring within 3 months of radiosurgery) and various factors associated with early complications following stereotactic Gamma Knife radiosurgery for intracranial lesions. Patients and Methods: Seventy-nine previously unirradiated consecutive adult patients (82 lesions: arteriovenous malformations 35, benign tumors 43, metastases 4) treated by Gamma Knife radiosurgery were studied between May 1997 and August 1998. The median target volume was 4.8 cm3. The median dose of 15 Gy was prescribed to the 50% isodose. Patients were evaluated clinically and radiologically (with CT/MRI/SPECT) at 3-month intervals for the 1st year and 6 monthly thereafter. Complications were further divided as immediate (occurring within 24 h) or acute (occurring from 1 day to 3 months). Results: Early complications were observed in 19/79 (24.0%) patients. These included immediate in 10 (12.7%) and acute complications in 9 (11.3%) patients and were characterized by headache, nausea/vomiting, vertigo and seizures. No severe early complications were observed. Radiological changes in the form of perilesional edema were seen in 8/82 (9.8%) lesions. Maximum target diameter >25 mm was the only factor significantly associated with early complications by univariate analysis (p = 0.0335). Multivariate analysis revealed maximum target diameter >25 mm and prescribed dose >20 Gy to be significantly associated with early complications (p = 0.0442 and p = 0.0083, respectively). Conclusion: Up to one fourth of the patients undergoing Gamma Knife radiosurgery for intracranial lesions can experience self-limiting early toxicity. The selection of targets with small diameter and volume may reduce the risk of early complications following Gamma Knife radiosurgery.

Atypical teratoid rhabdoid tumor of the brain: case series and review of literature

IntroductionIntracranial atypical teratoid rhabdoid tumor is an uncommon malignancy with a dismal outcome. Commonly misdiagnosed over the decades as primitive neuroectodermal tumor of the brain, it has dramatically different biological behavior.DiscussionWe herein report a case series of five patients diagnosed and treated as atypical teratoid rhabdoid tumor of the brain in a major cancer center in north India. We have also analyzed the clinical, histopathological, and radiological features and the therapeutic options of this enigmatic tumor.

Radiation Induced Lung Injury: Prediction, Assessment and Management

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (<6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and pro- fibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

F-18 FDG PET-CT for predicting survival in patients with recurrent glioma: a prospective study.

IntroductionRecurrent gliomas are usually histologically high grade; either due to recurrence of a de novo high-grade primary or anaplastic transformation in case of low-grade tumors. Survival in these patients is variable. The objective of the present study is to evaluate the role of FDG PET-CT for predicting survival in a large group of patients with suspected recurrent glioma.MethodsA total of 81 previously treated histopathologically proven glioma patients; with clinical and conventional imaging findings suspicious of recurrence were included in this study. All patients underwent FDG PET-CT study. Based on tumor to white matter (T/W) and tumor to grey matter (T/G) ratios, all lesions were scored on PET-CT (PET scores 0, 1 and 2). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was done for each variable employing univariate analysis followed by multivariate analysis, using variables found significant on univariate analysis.ResultsPET score was found to be the most significant predictor of survival in univariate and multivariate analysis (p 0.003). Patients having PET score 2 had poorer survival compared to both PET score 0 (p 0.001) and PET score 1 (p 0.004). Other covariates found to have significant correlation with survival were primary treatment modality and clinical symptoms at the time of recurrence.ConclusionFDG uptake on PET-CT is a strong predictor of survival in patients with suspected recurrent glioma.

Normal tissue complication probability of fibrosis in radiotherapy of breast cancer: accelerated partial breast irradiation vs conventional external-beam radiotherapy.

AIMS Radiotherapy forms an integral part of breast-conserving treatment in early-stage breast cancer. Subcutaneous fibrosis of the treated breast is an important late effect in whole-breast irradiation. The aim of this study was to compare the normal tissue complication probability (NTCP) for radiation-induced fibrosis in treated breast using accelerated partial-breast irradiation (APBI) vs conventional treatment. MATERIALS AND METHODS Ten postoperative early-stage breast cancer patients (T1N0M0) were included in this dosimetric analysis. APBI treatment was planned using conformal radiotherapy technique and conventional treatment plans included two tangential portals. All the APBI treatment plans were made with five non-coplanar beams with 6 MV photons. The prescription dose was 38 Gy in 10 fractions for the APBI treatments and 50 Gy in 25 fractions, followed by a boost dose of 16 Gy in 8 fractions, for the conventional treatments. We used Lymans relative-seriality model and the breast fibrosis NTCP model fitting parameters for the study. RESULTS The equivalent uniform dose (EUD) was 30.09 Gy and 50.79 Gy in APBI and conventional treatment, respectively. The mean NTCP values for ipsilateral breast fibrosis in APBI and conventional treatment were 0.51 and 25.66%, respectively. Using the paired t-test, a statistically significant difference was seen in the breast fibrosis NTCP values for APBI vs conventional treatment (P < 0.001). CONCLUSIONS APBI reduces the ipsilateral breast fibrosis compared to conventional whole-breast treatment in early-stage breast cancer.