Ten years survival results of randomized study comparing weekly vs. triweekly cisplatin with concurrent radiation in locally advanced carcinoma cervix.

Background: The current standard of treatment for locally advanced cervical cancer is concurrent chemo-radiation with improved overall survival (OS) by 6% with manageable toxicities. The cisplatin 40 mg/m2 given weekly is the widely practiced regimen for 4-6 cycles concurrently with irradiation. Materials and methods: Two hundred and twelve patients with histologically proven squamous cell carcinoma of cervix with stages IIB to IIIB were enrolled between 2007-2011. External beam radiation dose of 45 Gy in 25 fractions was delivered over 5 weeks. Brachytherapy was delivered by manual afterloading cesium-137 (Cs137) low dose brachytherapy (LDR) using modified Fletcher suit intracavitary applicators to a total dose of 30 Gy to Point A or interstitial template to dose of 21 Gy/3 fractions with remote afterloading iridium-192 (Ir192) high dose brachytherapy (HDR). Patients were randomized to arm A receiving 40 mg/m2 of concurrent cisplatin weekly and arm B receiving 100 mg/m2 of concurrent cisplatin triweekly. Results: One hundred and nine patients were randomized to weekly cisplatin and one hundred and three patients to triweekly cisplatin at the end of recruitment. At ten years, the OS was higher in the weekly arm (79.8%) compared to triweekly arm (70.9%). Disease free survival (DFS) was almost equal (76.1% and 73.8%) in the weekly and three-weekly arms. There is definite significance in overall DFS with patients receiving the cumulative cisplatin doses of more than 250 mg (p = 0.028). The patients with more than 45 years of age had better overall survival (OS) (79%) with statistical significance 31 (p = 0.020). Conclusion: Both cisplatin based triweekly and weekly concurrent chemotherapy are equally effective in terms of OS and DFS.

Weekly vs. tri-weekly cisplatin based chemoradiation in carcinoma cervix: a prospective randomized study of toxicity and compliance.

BACKGROUND: Addition of chemotherapy to radiation has improved 5-year survival by 6%. However, the optimal dose and schedule of concurrent cisplatin is not well defined, though widely accepted practice is the weekly schedule of 40 mg/m2 for 5 weeks. Repeated admissions for weekly cisplatin drain the limited resources in high volume centres. We intended to study the compliance and toxicity of two cisplatin schedules in our patients diagnosed with carcinoma cervix. MATERIALS AND METHODS: Between 2007-2011, 212 patients, histologically proven squamous cell carcinoma with stages IIB to IIIB were randomized into two arms. All patients were planned for external beam radiotherapy 45 Gy/25 frs over 5 weeks followed by Intracavitary or Interstitial brachytherapy to a total BED dose of 75-85 Gy. Single agent cisplatin given concomitantly, was scheduled weekly (40 mg/m2/cycle, 5 cycles) in an arm A and three weekly (100 mg/m2/cycle, 2 cycles) in an arm B. Toxicity and compliance were evaluated weekly according to the RTOG guidelines. Analysis of the compiled data was done using SSPS version 20. RESULTS: Of the evaluable 212, 109 patients received weekly cisplatin chemotherapy and 103 patients received three weekly cisplatin. The most common acute toxicity observed was grade I-II leucopoenia. The upper and lower gastrointestinal reactions were high in three weekly arms, which was statistically significant (57% and 42.7%, p < 0.05). Proctitis was observed in 10% of patients in both of the arms and only two patients had Gr1 Cystitis after 6 months of treatment. CONCLUSIONS: Tri-weekly cisplatin based concurrent chemoradiation can be adopted in high volume centres with manageable haematological and gastrointestinal acute toxicities.

Helical nanobots as mechanical probes of intra- and extracellular environments.

A rheological probe that can measure mechanical properties of biological milieu at well-defined locations with high spatial resolution, on a time scale faster than most biological processes, can further improve our understanding of how living systems operate and behave. Here, we demonstrate nanorobots actively driven in realistic ex vivo biological systems for fast mechanical measurements with high spatial accuracy. In the various demonstrations of magnetic nanobots as mechanical probes, we report the first direct observation of the internalization of probes by a living cell, the accurate measurement of the 'fluid phase' cytoplasmic viscosity of ~200 cP for a HeLa cell, demonstration of intracellular measurements in cells derived from human patients; all of which establish the strength of this novel technique for measurements in both intra- and extracellular environments.

A prospective randomized study comparing concurrent chemoradiation with weekly and 3 weekly cisplatin in locally advanced oropharyngeal carcinoma.

INTRODUCTION: The chemotherapy schedules with cytotoxic dose or weekly regimes are still challenging, weighing the benefits versus toxicities. This prospective randomized study is an attempt to assess the efficacy of two schedules of cisplatin in management of locally advanced HNSCC. OBJECTIVES: The objectives of this study was to evaluate tolerance, tumour response and toxicities of concurrent chemoradiation with cisplatin in weekly and three weekly regimes. METHODS: Locally advanced oropharyngeal squamous cell carcinoma patients fit for concurrent chemoradiation with cisplatin 40 mg/m2 (weekly) and 100 mg/m2 (3 weekly) were randomized to Arm A and B concurrently with radiotherapy of 70Gy/35frs/7 weeks. STATISTICAL ANALYSIS: Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale between the groups. The statistical software SPSS 15.0 was used. RESULTS: Between December 2010 and January 2013, 60 patients were enrolled. The median cycles of cisplatin in Arm-A was 5 and 2 in Arm-B. The complete response of 80.9% vs 75% and partial response of 14.3% vs 12.5% was observed in both arms respectively. There was no statistical difference in acute radiation and hematological toxicities between the two groups. With median follow up of 28 months, the 2 and 5 years overall survival was 55% and 58%; 41.6% and 32.3% in arms A and B respectively. CONCLUSION: In our study of locally advanced oropharyngeal carcinoma treated with radical radiotherapy comparing concurrent chemotherapy with cisplatin weekly vs 3 weekly had no significant difference in overall response, complete response and acute toxicities.

Dosimetric comparison of various optimization techniques for high dose rate brachytherapy of interstitial cervix implants.

HDR brachytherapy treatment planning often involves optimization methods to calculate the dwell times and dwell positions of the radioactive source along specified afterloading catheters. The purpose of this study is to compare the dose distribution obtained with geometric optimization (GO) and volume optimization (VO) combined with isodose reshaping. This is a retrospective study of 10 cervix HDR interstitial brachytherapy implants planned using geometric optimization and treated with a dose of 6 Gy per fraction. Four treatment optimization plans were compared: geometric optimization (GO), volume optimization (VO), geometric optimization followed by isodose reshape (GO_IsoR), and volume optimization followed by isodose reshape (VO_IsoR). Dose volume histogram (DVH) was analyzed and the four plans were evaluated based on the dosimetric parameters: target coverage (V100), conformal index (COIN), homogeneity index (HI), dose nonuniformity ratio (DNR) and natural dose ratio (NDR). Good target coverage by the prescription dose was achieved with GO_ IsoR (mean V100 of 88.11%), with 150% and 200% of the target volume receiving 32.0% and 10.4% of prescription dose, respectively. Slightly lower target coverage was achieved with VO_IsoR plans (mean V100 of 86.11%) with a significant reduction in the tumor volume receiving high dose (mean V150 of 28.29% and mean V200 of 7.3%). Conformity and homogeneity were good with VO_ IsoR (mean COIN = 0.75 and mean HI = 0.58) as compared to the other optimization techniques. VO_IsoR plans are superior in sparing the normal structures while also providing better conformity and homogeneity to the target. Clinically acceptable plans can be obtained by isodose reshaping provided the isodose lines are dragged carefully.