Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study.

OBJECTIVE: With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study. METHODS: Between May 2010 and April 2012, 150 histologically proven cervical cancer patients treated with radio (chemo) therapy were accrued. Cervical biopsies/brushings were collected at pre-treatment, end of treatment and at 3 monthly intervals up to 24months. Quantitative estimation of HPV 16/18 was done using real-time polymerase chain reaction (RT-PCR) and correlated with various clinical end-points. RESULTS: Out of 150 patients accrued, 135 patients were considered for final analysis. Pre-treatment HPV16/18 DNA was detected in 126 (93%) patients, with HPV-16 present in 91%. The mean log (±SD) HPV-16 and HPV-18 viral load at pre-treatment was 4.76 (±2.5) and 0.14 (±2.1) copies/10ng of DNA, respectively. Though significant decline in viral load was observed on follow-ups (p<0.0001); by 9-month follow-up, 89 (66%) patients had persistence of HPV infection. Patients with persistent HPV 16/18 infection had a significantly higher overall and loco-regional relapses [44/89 (49%) and 29/89 (32%)] as compared to HPV clearance by 9months [12/43 (28%) and 5/43 (11%)] with p=0.024 and p=0.02, respectively. Also, persistent HPV infection by 24-month showed a significant impact on loco-regional control (LRC) and recurrence-free survival (RFS). CONCLUSION: In locally advanced cervical cancers treated with radical radio (chemo) therapy, persistent HPV 16/18 infection is significantly high in immediate post-treatment period and correlated with higher loco-regional, overall relapses and was also associated with early relapses.

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PURPOSE: This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone. MATERIALS AND METHODS: Patients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery. RESULTS: A total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03). CONCLUSION: Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

18-fluoro-deoxy-glucose positron emission tomography with computed tomography-based gross tumor volume estimation and validation with magnetic resonance imaging for locally advanced cervical cancers.

PURPOSE: Anatomy and morphology-based imaging is routinely used for radiotherapy purpose to deliver precision treatment. There is an interest in using information from functional imaging for conformal radiation therapy planning. These functional imaging techniques need to be validated rigorously before their routine use. We attempted to evaluate and validate the use of 18-fluoro-deoxy-glucose positron emission tomography with computed tomography (¹8FDG PET-CT) on primary tumor of the cervical carcinoma, with an aim of arriving at a cutoff maximum standardized uptake value (SUVmax) at which the tumor volume correlates best with magnetic resonance imaging (MRI). This observational study was a part of an ethics committee-approved study evaluating pretreatment MRI and FDG PET-CT. MATERIALS AND METHODS: Patients' biopsy-proven cervical carcinomas (stages IIB and IIIB) were included in this study and underwent pretreatment MRI and FDG PET-CT as per institutional protocol. Volumes of the disease at the cervix on the MR image were calculated. Volumes at the FDG PET-CT scan at different percentages of SUVmax were auto contoured. Volume at MRI was correlated with each different percentage cutoff of the SUVmax. RESULTS: Data of 74 patients were available for the study. The mean (SD) SUVmax of the primary tumor was 15.7 (7.0). The mean MRI volume correlates significantly (P < 0.001) with 30% and 35% of SUVmax values with good correlation according to the Pearson bivariate correlation (r = 0.79 each). The mean difference between MRI and PET volumes was least with 30% SUVmax. CONCLUSIONS: ¹8FDG PET-CT SUV-based primary tumor volume estimation at 30% to 35% of SUVmax values correlates significantly with the criterion standard MR volumes for primary cervical tumor with squamous histology in our population.

Recurrence pattern with respect to two different dose fractionations in patients with locally advanced head and neck cancer treated with chemoradiation using image-guided volumetric arc therapy.

BACKGROUND: Patients with head and neck cancer were treated with either 70 Gy in 35 fractions (Arm A) or 66 Gy in 30 fractions (Arm B). MATERIALS AND METHODS: Total 168 patients of carcinoma oropharynx, larynx, and hypopharynx treated with radical chemoradiation in two Arm A versus B (65 vs. 103 patients). RESULTS: With a median follow-up of 16 months (0-67), 2 year disease-free survival (DFS) and overall survival (OS) was 56.3% versus 62.1% (p = 0.64) and 44.5% versus 53.0% (p = 0.51) in Arm A versus B. Total 22 (33.8%) versus 28 (27.2%) failed locoregionally. Majority of failures were infield for both primary (17 vs. 23 cases) and nodes (13 vs. 12) in Arm A versus B. Ten (71.4%) vs. 10 (76.9%) had nodal failure in index nodal level only. CONCLUSION: Commonly seen failure in head-neck radical chemoradiation is within infield high-risk volume, nodal failure being most common in index nodal level.

Serial Bone Density Changes in Women Undergoing Pelvic (Chemo) Radiation: Results From the PARCER Trial.

PURPOSE: Pelvic irradiation leads to substantial dose to the pelvic girdle. However, bone density loss as a function of radiation therapy dose and time has not been investigated. This study was undertaken to evaluate such a dose-response relationship. METHODS AND MATERIALS: Women undergoing pelvic radiation therapy for cervix cancer within a phase 3 trial were included. The study necessitated 2 computed tomography imaging sets acquired at least 12 months apart in patients with no evidence of relapse. All images were transferred to the treatment planning system to determine radiation dose and Hounsfield unit (HU). Across the entire lumbopelvic region (lumbar 1-5 [L1-5] vertebrae, pubic symphysis, femur, acetabulum, greater trochanter, and anterior-superior iliac spine) multiple regions were defined to measure radiation therapy dose and HU. Bone health was categorized as normal if >130 HU, osteopenic at 110 to 130 HU, and osteoporotic <110 HU at baseline and follow-up. Univariate analysis was performed to test the effect of various factors on HU. Further interaction among radiation therapy dose, time, and HU was assessed using a linear mixed model. RESULTS: Overall, 132 of 300 patients were eligible. The median age was 49 (42-56) years. With a prescription dose of 50 Gy, the L1 and L2 vertebrae received a median dose of 1.2 and 4 Gy, respectively, and L3-5 received 10 to 50 Gy. At 24 months, median HU loss at L4-5 was 45 HU (interquartile range, 34-77 HU). Out of the 132 patients, at baseline 96% had normal bone health. However, at the last follow-up, 3% of patients had normal bone health, 12% developed osteopenia, and 85% developed osteoporosis (P < .001). There were no patient- or treatment-related factors predicted for HU loss on univariate analysis. HU loss >60 to 70 was observed at >45 Gy at L5 vertebra (60-70 HU, P < .02) and >15 Gy at L4 vertebra (33 HU; P = .04). CONCLUSIONS: Dose-response relationship is observed between radiation dose and bone mineral density loss. Prospective studies are needed to corroborate these observations and design future interventions.

Patterns of Relapse After Adjuvant Chemoradiation for Cervical Cancer in a Phase 3 Clinical Trial (PARCER): An Evaluation of Updated NRG Oncology/RTOG Target Delineation Guidelines.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) under NRG Oncology recently published updated contouring guidelines for intensity modulated radiation therapy in postoperative treatment for endometrial and cervical cancer. The present study was designed to evaluate the implications of newly published guidelines. METHODS AND MATERIALS: We recruited 300 patients in a phase 3 randomized controlled trial of adjuvant chemoradiation therapy for cervical cancer (NCT01279135) to understand patterns of relapse. For those patients with pelvic relapse, we imported radiation therapy structure sets, treatment plans, and diagnostic images at relapse on the treatment planning system. We performed rigid registration with treatment planning images that contained the delineated planning target volume and radiation dose information. We delineated gross tumor volume at time of relapse on the diagnostic scans and superimposed it on the radiation therapy treatment scans. We categorized the site of pelvic relapse as "within field of old RTOG/[Postoperative Adjuvant Radiation in Cervical Cancer (PARCER)] target delineation guidelines" or "within field of new NRG/RTOG guidelines," or both, and compared proportions of recurrences contained within the 2 guidelines. We consider a P value of <.05 statistically significant. Additionally, we generated intensity modulated radiation therapy treatment plans based on the new guidelines for a limited set of patients to see if these new guidelines increased the organ at risk doses. RESULTS: Most common form of relapse was distant metastasis (15%). Pelvic relapse rate in our study was 8%. Overall, 9 out of 19 relapses were encompassed in the contouring guidelines of the old RTOG/ Postoperative Adjuvant Radiation in Cervical Cancer (PARCER) trial, and 12 out of 19 were encompassed within the new RTOG 2021 contouring guidelines. This corresponded to a further 1% reduction in local relapses (P = .007). Dose to rectum was marginally increased with the new contouring, with no difference in other organs at risk. Salvage treatment was offered in 25 out of 60 patients who relapsed. Patients who received local treatment after relapse had a mean survival after relapse of 27.2 months compared with 8 months among those who received supportive care alone. CONCLUSIONS: Our study supports the use of newly published NRG/RTOG contouring guidelines in patients with cervical cancer who have undergone hysterectomy. Further data are needed to ascertain if anterior extension of the clinical target volume is needed as in the Postoperative Adjuvant Radiation in Cervical Cancer trial.

Objective assessment of swallowing function after definitive concurrent (chemo)radiotherapy in patients with head and neck cancer.

The aim of this study was to objectively assess swallowing function and factors impacting it after curative intent definitive (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Swallowing function was studied in a cohort of 47 patients with locoregionally advanced (T1-4, N0-3) HNSCC treated with definitive CRT. Objective assessment of swallowing function was done using modified barium swallow (MBS) at baseline (pre-CRT) and subsequent follow-ups. Scoring of MBS was done using penetration-aspiration scale (PAS). Abnormal swallowing was defined in terms of incidence and severity of penetration-aspiration, pharyngeal residue, postural change, and regurgitation. Aspiration, residual, postural change, and regurgitation were present on baseline pre-CRT assessment in 9 (19%), 11 (23%), 10 (21%), and 5 (10%) patients that increased to 11 (29%), 11 (29%), 12 (32%), and 10 (26%) patients, respectively, at 6-month post-CRT evaluation. The proportion of patients with high PAS scores (3-7) increased from 27% at baseline to 37% at 6-month post-CRT evaluation. Among patients (n = 34) with low PAS scores (≤2) at baseline, additional impairment of swallowing function was seen in 53 and 46% at 2- and 6-month assessment, respectively. Residue (44%) and aspiration (18%) domains were impaired in a higher proportion of patients after CRT. Thin and thick barium had higher aspiration and residue function impairment, respectively. Patients with pre-CRT poor subjective swallowing function (P = 0.004), hypopharyngeal primary (P = 0.05), and large tumor volume (P = 0.05) had significantly worse objective swallowing function at baseline as demonstrated by pretreatment PAS scores. This study provides useful information regarding patterns of objective swallowing dysfunction in patients treated with definitive (chemo)radiotherapy. There is significant impairment of objective swallowing function in all domains following CRT, with residue and aspiration domains being affected most significantly.

Outcomes of locally advanced cervical cancer presenting with obstructive uropathy: An institutional audit.

BACKGROUND: There is paucity of outcome data of patients with cervical cancer presenting with malignant obstructive uropathy. The present retrospective study describes outcomes of patients with cervical cancer who presented with obstructive uropathy at the time of diagnosis and underwent urinary diversion with percutaneous nephrostomy (PCN) before/during treatment. METHODS: Patients who underwent PCN from January 2010 to June 2015 were included. Intent of treatment (radical or palliative) was decided within multidisciplinary team depending on disease stage, Karnofsky performance status (KPS), and degree of renal derangement. Treatment and outcome details were retrieved from electronic records. Time to normalization of creatinine, feasibility of delivering planned treatment, and overall survival (OS) were determined. Impact of various prognostic factors on outcomes was determined using univariate or multivariate analysis. RESULTS: After PCN and double-J stenting, 50% were eligible for (chemo) radiation. All radically treated patients (26/52) received brachytherapy. The median EQD2 to point A was 78 Gy (72-84 Gy). The median OS was 10 (0.5-60) months. Patients who completed chemoradiation had median OS of 31 months. Those receiving radical radiation and palliative radiation had median OS of 11 and 6 months, respectively. On univariate analysis, smaller tumor size (p = 0.03), high KPS (P = 0.04), and radical intent of treatment (P = 0.05) predicted for OS. CONCLUSION: Patients presenting with obstructive uropathy have median OS less than a year despite urinary diversion. Select cohort with good performance status, small tumor size, and serum creatinine of ≤3 mg/dL may be selected for diversion procedures and potential radical treatment.

Treatment planning of epithelial ovarian cancers using helical tomotherapy.

Whole Abdomen Radiotherapy (WAR) for epithelial ovarian cancer though effective has been used sparingly due to inadequate target coverage and poor sparing of Organ At Risk (OAR) leading to significantly higher toxicities. Newer radiation techniques have shown potential for significant improvement in the therapeutic ratio. The purpose of this study was to evaluate Helical Tomotherapy(HT) for WAR. The objective parameters were to obtain uniform and adequate target coverage with maximum OAR sparing. HT plans were generated for five patients with field-width of 5.0/2.5 cm, modulation factor of 3.5/3.0, and a pitch of 0.3. A dose of 25 Gy in 25 fractions was prescribed to the abdomen with a simultaneous boost of 45 Gy in 25 fractions to the pelvis. Dose-volume parameters and various indices were analyzed and compared. Mean volume (standard-deviation) of abdominal and pelvic PTV (planning target volume) was 6630 +/-450 cm3 and 1235 +/-98 cm3 respectively. Mean length of PTV in cranio-caudal direction was 41+/-4 cm. Volume receiving 95% and 107% of the prescription dose, (V95% and V107%) was 95.6+/-2.7% and 2.6+/-0.5% for abdominal-PTV, and 95.7+/-2.4% and 0% for pelvic-PTV respectively. Homogeneity and Conformity indices were 17.5+/-1.7, 1.2+/-0.03 for abdominal PTV, and 5.2+/-0.7, 1.1+/-0.02 for pelvic-PTV respectively. Median dose received by the kidneys, liver and bone marrow were 9.6+/-1.2 Gy, 17+/-2.7 Gy and 22+/-1.4 Gy respectively. HT achieves an excellent coverage of WAR target with simultaneous pelvic boost and better organ (kidneys and liver) sparing. HT for WAR has the potential as consolidative therapy which is being evaluated further in a phase II cohort study in epithelial ovarian cancers.

A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy.

PURPOSE: A treatment planning study was performed to evaluate the performance of the novel volumetric modulated single arc radiotherapy on cervix uteri cancer patients. Conventional fixed field IMRT was used as benchmark. METHODS AND MATERIALS: CT datasets of eight patients were included in the study. Plans were optimised with the aim to assess organs at risk and healthy tissue sparing while enforcing highly conformal target coverage. Planning objectives for PTV were: maximum significant dose lower than 52.5 Gy and minimum significant dose higher than 47.5 Gy. For organs at risk, the median and maximum doses were constrained to be lower than 30 (rectum), 35 (bladder) and 25 Gy (small bowel) and 47.5 Gy; additional objectives were set on various volume thresholds. Plans were evaluated on parameters derived from dose volume histograms and on NTCP estimates. Peripheral doses at 5, 10 and 15 cm from the PTV surface were recorded to assess the low-level dose bath. The MU and delivery time were scored to measure expected treatment efficiency. RESULTS: Both RapidArc and IMRT resulted in equivalent target coverage but RapidArc had an improved homogeneity (D(5%)-D(95%) = 3.5 +/- 0.6 Gy for RapidArc and 4.3 +/- 0.8 Gy for IMRT) and conformity index (CI(90%) = 1.30 +/- 0.06 for RapidArc and 1.41 +/- 0.15 for IMRT). On rectum the mean dose was reduced by about 6 Gy (10 Gy for the rectum fraction not included in the PTV). Similar trends were observed for the various dose levels with reductions ranging from approximately 3 to 14.4 Gy. For the bladder, RapidArc allowed a reduction of mean dose ranging from approximately 4 to 6Gy and a reduction from approximately 3 to 9 Gy w.r.t. IMRT. Similar trends but with smaller absolute differences were observed for the small bowel and left and right femur. NTCP calculations on bladder and rectum confirmed the DVH data with a potential relative reduction ranging from 30 to 70% from IMRT to RapidArc. The healthy tissue was significantly less irradiated in the medium to high dose regions (from 20 to 30 Gy) and the integral dose reduction with RapidArc was about 12% compared to IMRT. Concerning peripheral dose, the relative difference between IMRT and RapidArc was of 9 +/- 2%, 43 +/- 11% and 36 +/- 5% at 5, 10 and 15 cm from the PTV surface, respectively. The MU/Gy from RapidArc was 245 +/- 17 corresponding to an expected average beam on time of 73 +/- 10 s per fractions of 2 Gy. IMRT plans presented higher values with an average of MU/Gy = 479 +/- 63. CONCLUSION: RapidArc was investigated for cervix uteri cancer showing significant improvements in organs at risk and healthy tissue sparing with uncompromised target coverage leading to better conformal avoidance of treatments w.r.t. conventional IMRT. This, in combination with the confirmed short delivery time, can lead to clinically significant advances in the management of this highly aggressive cancer type. Clinical protocols are now advised to evaluate prospectively the potential benefit observed at the planning level.

Prognostic factors in node negative premenopausal women treated with breast conserving therapy without adjuvant systemic therapy.

PURPOSE: To study the prognostic factors in node negative premenopausal women treated with breast conserving therapy (BCT) without any adjuvant systemic therapy. METHODS: Of the 1022 women treated with BCT at Tata Memorial Hospital, there was a cohort of 175 women who were premenopausal, node negative and had not received any adjuvant systemic therapy. BCT consisted of wide excision, complete axillary clearance, whole breast radiotherapy (45 Gy in 25 fractions) with 6 MV photons plus tumour bed boost either with brachytherapy or electrons. RESULTS: The median age at presentation was 38 years (range 22-51 years) and the median pathological tumour size was 3 cm (1-5 cm). The 5-year actuarial local control rate was 89.5% and the overall survival (OS) was 88%. On univariate analysis, lymphovascular invasion (LVI) was the only prognostic factor affecting all failures and disease-free survival. The 5-year local control rate in absence of LVI was 93.5% in contrast to 76.5% (p=0.0098) when LVI was present. Similarly, the OS in absence of LVI was 91% in contrast to 74% in presence of LVI (p=0.02). On multivariate analysis, LVI was the independent prognostic factor affecting the disease-free survival (p=0.001; 95% CI: 1.46-4.96). CONCLUSION: LVI emerged as the most important prognostic factor for node negative premenopausal women not receiving adjuvant systemic therapy. There is a need to take into consideration the presence of LVI while deciding adjuvant systemic therapy in T1N0 patients.

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.

Standard Chemoradiation and Conventional Brachytherapy for Locally Advanced Cervical Cancer: Is It Still Applicable in the Era of Magnetic Resonance-Based Brachytherapy?

Purpose Recent guidelines recommend magnetic resonance imaging-based brachytherapy (MRBT) for locally advanced cervical cancer. However, its implementation is challenging within the developing world. This article reports the outcomes of patients with locally advanced cervical cancer treated with chemoradiation and point A-based brachytherapy (BT) using x-ray- or computed tomography-based planning. Methods Patients treated between January 2014 and December 2015 were included. Patients underwent x-ray- or computed tomography-based BT planning with an aim to deliver equivalent doses in 2 Gy (EQD2) > 84 Gy10 to point A while minimizing maximum dose received by rectum or bladder to a point or 2 cc volume to < 75 Gy EQD2 and < 90 Gy EQD2, respectively. The impact of known prognostic factors was evaluated. Results A total of 339 patients were evaluated. Median age was 52 (32 to 81) years; 52% of patients had stage IB2 to IIB and 48% had stage III to IVA disease. There was 85% compliance with chemoradiation, and 87% of patients received four or more cycles. Median point A dose was 84 (64.8 to 89.7) Gy. The median rectal and bladder doses were 73.5 (69.6 to 78.4) Gy3 and 83 (73.2 to 90.0) Gy3, respectively. At a median follow-up of 28 (4 to 45) months, the 3-year local, disease-free, and overall survival for stage IB to IIB disease was 94.1%, 83.3%, and 82.7%, respectively. The corresponding rates for stage III to IVA were 85.1%, 60.7%, and 69.6%. Grade III to IV proctitis and cystitis were observed in 4.7% and 0% of patients, respectively. Conclusion This audit demonstrates good 3-year outcomes that are comparable to published MRBT series. Conventional BT with selective use of interstitial needles and MRBT should continue as standard procedures until level-I evidence for MRBT becomes available.

Incidental Dose to Pelvic Nodes in Bladder-Only Radiotherapy: Is It Clinically Relevant?

BACKGROUND AND PURPOSE: Although there is a strong biological rationale to electively treat the pelvic nodes during bladder preservation, its clinical benefit is uncertain. This may be explained by the incidental dose received by the nodal regions when treating the bladder alone. This study was conducted to investigate the doses received by the different pelvic nodal regions when the bladder alone is treated by standard conformal radiotherapy. METHODS AND MATERIALS: The computed tomography data sets of 20 patients with node-negative muscle-invasive bladder cancer treated in a bladder preservation protocol were studied. Patients were originally treated with conformal radiotherapy to the bladder alone. Replanning was done with additional delineation of the pelvic nodal regions namely common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose volume parameters such as Dmean, Dmax, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. RESULTS: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator, external iliac, and internal iliac regions was 59, 45, and 36 Gy, respectively. The dose received by these 3 regions in the full bladder state was 63, 52, and 47 Gy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. CONCLUSION: The incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation, possibly enough to influence micrometastatic disease. This may be a reason for the lack of clear benefit seen with nodal irradiation in bladder cancer. Advances in Knowledge: This study highlights that the incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation. The obturator nodes received the highest dose among all nodal regions with mean dose of 59 Gy.

Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy.

OBJECTIVES: Pelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy. METHODS AND MATERIALS: Twenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose-volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. RESULTS: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. CONCLUSION: The incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

Income generated by women treated with magnetic resonance imaging-based brachytherapy: A simulation study evaluating the macroeconomic benefits of implementing a high-end technology in a public sector healthcare setting.

PURPOSE: To estimate the difference in income generated if all women presenting in our institute over a 5-year period were treated with MRI-based image-guided brachytherapy (MR-IGBT) instead of conventional radiograph-based brachytherapy (CR-BT). METHODS AND MATERIALS: Outcome data from 463 patients (94 treated with MR-IGBT) treated in our institute was used to simulate cumulative women-days of work and cumulative income over 5 years for 5526 patients expected to be treated in this period. The average daily income for a woman was derived from the National Sample Survey Organization (NSSO) survey data. Outcomes from both unmatched and propensity score-matched data sets were simulated. RESULTS: The cumulative income in 5 years ranged between Rs 101-168 million if all patients presenting at our institute underwent MR-IGBT. The simulated excess income ranged from Rs 4-45 million after 5 years, which represented 6-66% of the expenditure incurred for acquiring the required equipment and manpower for practicing exclusive MR-IGBT. CONCLUSIONS: Using outcome data from a prospective cohort of patients treated with MR-IGBT in our institute, we demonstrated that significant economic gains may be realized if MR-IGBT was used instead of CR-BT.

Clinical outcome of high-dose-rate interstitial brachytherapy in vulvar cancer: A single institutional experience.

PURPOSE: With an aim to evaluate and report high dose date interstitial brachytherapy (HDR-ISBT) in vulvar cancers, we undertook this retrospective analysis. METHODS AND MATERIALS: Histologically proven vulvar cancers treated with HDR-ISBT between 2001 and 2016 were analyzed. Radiotherapy details, clinical outcome in terms of local control rates, survivals, and toxicities were evaluated. RESULTS: A total of 38 patients received HDR-ISBT, with definitive radiation in 29 (76.3%), adjuvant postoperative in six (15.8%) and salvage radiation in three (7.9%) patients. Of them, 29 patients received brachytherapy boost and nine patients ISBT alone. BT procedure included freehand plastic tube technique in 23 (single [n = 5] or multiple plane [n = 18]), 13 patients with template based and two patients combined approach. Patients with brachytherapy alone received median EQD2 of 38.4 Gy10 (35.5-46.7 Gy10), as boost received median 23.3 Gy10 (13-37.3 Gy10). At 3-month post-treatment response evaluation, 30 patients achieved clinically complete response, two patients partial response and six maintained postoperative status. With a median follow-up of 30 months, 29 (76.3%) were disease free, and 9 (23.7%) patients had relapsed disease with four patients expired due to disease and two died of other causes. The 5-year overall survival, disease free survival, and local control rates were 82%, 51%, and 77%, respectively. CONCLUSIONS: HDR-ISBT in vulvar cancer is a feasible and a viable option with acceptable and comparable outcomes.

High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience.

BACKGROUND: We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. METHODS: From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. RESULTS: Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). CONCLUSIONS: Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas.