The tolerance to chemoradiation for cervical cancer patients: A comparative prospective study of rural versus urban population.

Context: Rural versus urban cervical cancer. Aims: This study aims to study the difference in toxicities and clinical outcome of chemoradiation in urban and rural cervical cancer patient. Settings and Design: This was a prospective study. Subjects and Methods: In a double-arm prospective study, cervical cancer patients were treated with chemoradiation followed by brachytherapy. Patients were monitored weekly for hematological, gastrointestinal toxicities, and electrolyte imbalance. Acute toxicities and long-term outcome were compared between the two groups. Statistical Analysis Used: Kaplan-Meier survival curves for analysis of disease free and overall survival and Pearson's Chi-square test and Fisher's exact tests for analysis of toxicities were used. Results: Fifty-seven patients from urban and 114 from rural region were studied. There were no difference between the two groups as far as the patient characteristics, overall treatment time (OTT), hematological, electrolyte imbalance, local control, and disease-free survival between the two groups. Associated comorbidities were significantly higher (53% vs. 17%) with P < 0.0001 in urban population. Grade II and III enteritis were significantly higher 15.78% versus 21.05% (P = 0.00001) and 12.28% versus 11.40% (P = 0.03) in urban patients, respectively. Conclusions: Tolerance to chemoradiation, disease-free survival, and overall survival are similar in both urban and rural patients of cervical cancer, with more enteritis in urban group. However, this did not increase OTT.

Equivalent dose in 2 Gy (EQD2) to pelvic lymph nodes using volume based prescription for three brachytherapy applicators - a dosimetric retrospective analysis.

BACKGROUND: Pelvic lymph node (PLN) metastasis has been included in the FIGO staging, so there is a need to determine the dose contribution from brachytherapy to ascertain the total delivered dose to the pelvic lymph nodes in cervical cancer. The aim of the study was to calculate the equivalent dose in 2 Gy (EQD2) of the pelvic lymph nodes (PLNs) based on volume prescription using three applicators. MATERIALS AND METHODS: Forty-one patients who had undergone external beam radiotherapy followed by brachytherapy using tandem ovoids (TO), tandem ring (TR) and TO + free hand interstitial needles (TO + FH) applicators were taken for this study. 26 Gy in 4 fractions was prescribed to HRCTV. The external iliac node (ELN), internal iliac node (ILN) and obturator (OBT) were contoured and the median EQD2 of the lymph nodes was calculated. RESULTS: The median bilateral EQD2 values of ELN were 1.55 Gy (TR), 1.75 Gy (TO), 1.9 Gy (TO + FH), of ILN these were 2.57 Gy (TR), 3.27 Gy (TO), 3.04 Gy (TO + FH), and of OBT these were 3.69 Gy (TR), 4.46 Gy (TO), 4.69 Gy (TO + FH), respectively. The total median EQD2 values of TR, TO and TO + FH were 52.71 Gy, 53.03 Gy, and 53.88-62.73 Gy, respectively. CONCLUSION: Our study calculated the median EQD2 to the pelvic lymph nodes using three types of applicators in brachytherapy. This could serve as reference to decide on the EBRT boost dose while treating patients with enlarged pelvic lymph nodes.

Inter-institutional comparison of treatment practice for cervical cancer with special emphasis on brachytherapy.

PURPOSE: To compare the cervical cancer treatment outcome and toxicities between two different institutions. MATERIAL AND METHODS: We analysed the clinical outcome of cervical cancer patients treated at two different centres from January 2015 to December 2016. Centre A treated 72 patients by external beam radiotherapy (EBRT) to a dose of 45 Gy in 25 fractions followed by intracavitary brachytherapy (ICBT) 6.5 Gy × 4 fractions and centre B treated 89 patients by EBRT to a dose of 50.4 Gy in 28 fractions followed by ICBT 9 Gy × 2 fractions. The local control, distant metastases and treatment toxicities were compared. RESULTS: The median follow-up in centre A was 12 months and in centre B was 18 months. The median overall treatment time in centre A was 52 days and in centre B was 61 days. The mean equieffective doses in 2 Gy (EQD2) for high risk target volume (CTVHR) and point A in centre A were 84.59 and 64.5 Gy, respectively. The mean EQD2 for point A in centre B was 78.5 Gy. One patient out of 72 (1.38%) had local recurrence in centre A and five patients out of 89 (5.6%) had local recurrence in centre B. Local control in centre A was 98.6% and in centre B was 94.3%. The local recurrence rate was higher in centre B but it was not statistically significant (p = 0.15). One patient developed brain metastasis in centre B. One patient developed grade 3 proctitis in centre A. CONCLUSIONS: A high dose rate brachytherapy fractionation schedule of 6.5 Gy × 4 fractions over 2 days for CTVHR is associated with reduced overall treatment time, a slightly higher local control rate and lesser dose to OARs compared to 9 Gy × 2 fractions given one week apart to point A.

Implications of bladder volume on target coverage and dose to critical structures during high dose rate intracavitary brachytherapy for cervical cancer: A dosimetric study.

BACKGROUND: The distension of the bladder during intracavitary brachytherapy (ICBT) affects the applicator position and in turn the dose to tumour and normal structures. AIMS AND OBJECTIVES: To quantify the changes in the dose to high risk clinical target volume (HRCTV) and organs at risk (OARs) due to bladder filling. METHODS AND MATERIALS: In this prospective study, dosimetric parameters of 40 cervical cancer patients treated with (ICBT) were studied. Two sets of CT images with empty and bladder filled with 100 ml of contrast were used for analysis of doses to HRCTV and organs at risk OARs. The distance between posterior wall of the bladder and reference point on the flange was recorded in X,Y and Z. RESULTS: Target coverage between bladder distension and empty bladder was 84.15 vs 84.85 % (P=0.003) respectively. Mean dose to bladder was 1.57vs 2Gy (P=0.000), median dose was 6 vs7.25Gy (P=0.000), D5cc was 3.94 vs 4.17 Gy (P=0.103) and D2cc was 4.5 vs 5 Gy (P=0.01) respectively. The doses to rectum was D2cc - 3.76 vs 4.07Gy (P=0.000), Sigmoid was D2cc - 2.18 vs 2.43Gy (P=0.005), bowel D2cc was 2.81 vs 3.43Gy (P=0.000). The mean distance of the posterior wall of the bladder from reference point was 0.042 vs -0.079cm (P=0.391) in the X-axis, -0.618 vs -0.630cm (P=0.603) in Z-axis and 0.19 vs 0.26cm (P=0.009) in the Y-axis between two status of the bladder. CONCLUSIONS: Smaller volume of bladder receive higher dose and larger volumes a lower dose with bladder distension, while dose is same for rectum, sigmoid and bowel. The applicators shift posteriorly when the bladder is distended.

Compliance with bladder protocol during concurrent chemoradiation for cancer of the cervix and its impact on enteritis: A prospective observational study.

AIM: This prospective study aims to assess the compliance with bladder protocol and the correlation with enteritis during pelvic radiation. BACKGROUND: Bladder protocol is routinely used for patients undergoing pelvic radiation to reduce radiation enteritis. It is very difficult to maintain constant volume especially in the last two weeks due to radiation enteritis and cystitis. MATERIALS AND METHODS: Histologically proven 35 cervical cancer patients treated with concurrent chemoradiation in a tertiary care center were the subjects of this prospective study. Following CT simulation and after every fraction, patients were asked to void urine in a calibrated urine container and the volume was documented. Patients were assessed for the highest grade of radiation enteritis weekly as per common toxicity criteria. The mean voided urine volume was correlated with the radiation enteritis. RESULTS: The mean urine volume at planning CT scan was 295.85 ± 300 ml (SD) with a range of 75-650. At the end of treatment, it was reduced to 233.14 ± 250 ml (range 50-400 ml), a reduction by 21% (p < 0.001). The maximum grade of enteritis was grade I (11%), II (11.4%), III (3-29%) in week 1,2 and 3-5, respectively with a p value of <0.001. A mean urine volume of 230 ml was associated with grade III enteritis in the third week. CONCLUSIONS: Urine output volume measured using a calibrated container is a simple, efficient and practical method to monitor bladder distension thereby reducing enteritis in cervical cancer patients treated with concurrent chemoradiation.

Comprehensive assessment of Somnolence Syndrome in patients undergoing radiation to the brain.

AIM: The aim of this prospective study was to assess Somnolence Syndrome (SS) in patients undergoing radiation to the brain. BACKGROUND: SS is one of the sequelae of radiation to the brain, which is observed within three months of radiation. This is a self-limiting condition and a failure to diagnose leads to unnecessary investigations. This study was undertaken to objectively and subjectively analyze the occurrence, clinical presentation and severity of SS. MATERIALS AND METHODS: Thirty-three patients receiving radiation to the brain were included in the study. Visual Analog Scale (VAS) was used for subjective assessment and the Littman Somnolence Syndrome (LSS) scale was used for objective assessment of SS. Sleep Latency Test (SLT) was used to quantify SS. RESULTS: VAS scores showed an initial fall until week 3, followed by a plateau and a sudden increase after week 10. LSS scale at week 11 and 12 showed that 13 patients (43.3%) had grade 2, 5 (16.7%) had grade 3; and 2 (6.7%) had grade 4 SS. SLT revealed a shift of predominant sleep pattern from NREM 1 to NREM 2 at 6 weeks after radiation with a p value of 0.0412. CONCLUSIONS: An insight into SS, its features, frequency of occurrence and self limiting nature can prevent anxiety and unwarranted investigations in the immediate post radiation period.

The nuances of brachytherapy taught by teachers from beyond: Questionnaire-based assessment of the first cadaveric hands-on brachytherapy workshop in India.

PURPOSE: A questionnaire-based assessment of a cohort of young radiation oncologists attending the first human cadaveric hands-on brachytherapy workshop in India. METHODS AND MATERIALS: The cadaveric workshop for hands-on training in head/neck and gynecologic cancers was a novel process conducted at M.S. Ramaiah Medical College and Hospital, for which 30 attendees from all regions of India took part with an opportunity to interact with experienced resource persons, individually perform the procedure, and indulge in all aspects of brachytherapy process. The questionnaire was part of the workshop and enquired on common practices for head/neck and gynecologic brachytherapy followed by the attendees at their hospitals and their opinion on avenues for learning the skill of brachytherapy and its future as a therapeutic modality. RESULTS: Twenty-seven of thirty attendees were practicing brachytherapy at their centers out of which only 14 (46%) were doing head/neck brachytherapy. In gynecologic procedures, 89% were performing only intracavitary brachytherapy. Twenty attendees (66%) felt lack of expertise was the primary reason for dwindling brachytherapy practice in India. Ten (33%) of them felt that advancements in external radiotherapy were the second major cause for it. Some less important reasons given were lack of suitable cases, fear of toxicity, and reduced remuneration. CONCLUSIONS: Cadaveric brachytherapy workshops may be a practical and cost-effective method to inculcate this unique skill set in the next generation of radiation oncologists. This questionnaire-based assessment has tried to validate this opinion.

Does fall in serum glutathione predict the long-term outcome to concurrent chemoradiation for cervical cancer patients?

BACKGROUND: Wide variations are seen in clinical practice with respect to response to concurrent chemo radiation among cervical cancer patients. Fall in serum glutathione (GSH) level directly correlates with early response to treatment. Whether this early response translates to a better long term outcome is the subject of this prospective study. MATERIALS AND METHODS: Thirty eight women with cervical cancer were treated with concurrent chemo radiation followed by brachytherapy. Serum GSH was measured before and after two fractions of radiation and first chemotherapy. Patients were followed for a median follow up of four years. Fall in GSH was correlated with response at six weeks and disease status at four years. RESULTS: Median fall in serum GSH was 171.16 µg per ml. Fall in GSH was 170.42, 103.54 and 37.25 µg per ml (P value of <0.0001, 0.05 and 0.18) in patients showing complete response, partial response and no response respectively. Among 26 patients who had no disease at six weeks, 22 women remained disease free at four years (P < 0.0001), two recurred (P < 0.05) and two died of other causes respectively. Non bulky tumours and patients more than 50 years of age showed a fall of 190.69, 265.17 µg per ml respectively. CONCLUSION: Greater fall in serum GSH predicts better early response as well as long term disease control.

Comparison of manual and inverse optimisation techniques in high dose rate intracavitary brachytherapy of cervical cancer: A dosimetric study.

AIMS AND OBJECTIVES: To compare dosimetrically the manual optimisation with IPSA using dose volume histograms (DVH) among patients treated for carcinoma of cervix with intracavitary brachytherapy. BACKGROUND: With the advent of advanced imaging modalities, there has been a shift from conventional X-ray based planning to three-dimensional planning. Manual optimisation is widely used across various institutions but it is time consuming and operator dependant. Inverse planning simulated annealing (IPSA) is now available in various brachytherapy planning systems. But there is a paucity of studies comparing manual optimisation and IPSA in treatment of carcinoma cervix with intracavitary brachytherapy and hence this study. MATERIALS AND METHODS: Fifteen consecutive patients treated between December 2013 and March 2014 with intracavitary brachytherapy for carcinoma of cervix were selected for this study. All patients were initially treated with external beam radiotherapy followed by intracavitary brachytherapy. The DVH was evaluated and compared between manually optimised plans and IPSA in the same set of patients. RESULTS: There was a significant improvement in the HRCTV coverage, mean V100 of 87.75% and 82.37% (p = 0.001) and conformity index 0.67 and 0.6 (p = 0.007) for plans generated using IPSA and manual optimisation, respectively. Homogeneity index and dose to the OARs remained similar between the two groups. CONCLUSION: The use of inverse planning in intracavitary brachytherapy of cervix has shown a significant improvement in the target volume coverage when compared with manual planning.