Can Pretreatment MRI and Planning CT Radiomics Improve Prediction of Complete Pathological Response in Locally Advanced Rectal Cancer Following Neoadjuvant Treatment?

OBJECTIVE(S): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT. METHODS: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals. RESULTS: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66. CONCLUSION: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies.

Development and validation of a novel scoring system to predict the risk of uterine perforation during intracavitary brachytherapy for cervical cancer.

OBJECTIVE: To develop and validate a novel scoring system for predicting the risk of uterine perforation during brachytherapy (BT) in cervical cancer patients and to stratify patients based on this score to guide the use of ultrasound guidance during BT. METHODS: Fifty patients with uterine perforation during BT between January 2018 and December 2020 were included. Common reasons for perforation were identified and a scoring system was developed. This was then applied to a cohort of 50 patients without perforation. The 2 cohorts were compared using the χ² test. To validate the scoring system, all newly diagnosed patients who underwent BT in 2021 were scored, and analysed using χ² test and receiver operator characteristic curves. RESULTS: The mean score in the test cohort was 10.16 (range=7-14) and 5.92 (range=5-8) for patients with and without perforation. In the validation cohort, the mean score was 6.9 (range=5-10) and 9.33 (range=7-11) for those with and without perforation. Patients with a score <8 were classified as low risk, while those with a score ≥8 were classified as high risk. Among the criteria evaluated for validation, response to external beam radiotherapy, uterine position, cervico-uterine angle (uterine flexion), identification of cervical os at BT assessment, and the total score were significant predictors, while previous history of perforation, uterine length, and additional uterine anomaly were not. CONCLUSION: The novel scoring system is an effective predictor of perforation risk during BT. Implementing this during BT assessment can optimize the need for ultrasound guidance during the procedure.

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma.

Introduction: Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis. Methods and Materials: Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed. Results: As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values. Conclusion: SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease.

Outcomes of Squamous Cell Carcinoma Anal Canal treated with IMRT-VMAT-based Concurrent Chemoradiation: a Single Institutional Experience.

INTRODUCTION: Chemoradiation is the standard of care in locally advanced carcinoma of the anal canal. However, the irregular surface and elective inguinal treatment poses a challenge for radiation planning and treatment with associated significant toxicity. In this retrospective study, we analysed the outcome of patients treated with intensity-modulated radiation therapy (IMRT) at our centre from 2012 to 2019. METHODS AND MATERIALS: Records of patients treated with IMRT at our centre from 2012 to 2019 were reviewed. Patients with non-squamous histology and previous irradiation were excluded. Thus, 25 patients were found suitable for the study. RESULTS: Twenty-five patients with squamous cell carcinoma of the anal canal were treated at our centre from 2012 to 2019 using IMRT based chemoradiation. RTOG guidelines were followed for contouring and Varian Eclipse version 13(Palo Alto, California) was used for planning. Clinical response could be assessed in 20 patients and dosimetric data of all patients was available for review. The target volumes coverage goals as per ICRU 83 were achieved in all patients. The organ at risk constraints for bladder and femoral heads as per LATE-QUANTEC were achieved in most patients; however, the constraints for the rectum, testis and bowel bag were not achieved in the majority of the patients. The median duration of treatment break was 7 days. Mitomycin C and 5-FU or capecitabine were given concurrently with radiation. Eighteen patients (72%) received 2 cycles of chemotherapy, three (12%) received 1 cycle of chemotherapy while 4(16%) patients did not receive any chemotherapy. Median follow-up was 7.5 months. At median follow-up, 15(75%) patients were disease-free and asymptomatic, 2(10%) had residual disease and 3(15%) had progressive disease. Toxicity was assessed using CTCAE Version 5.0. Grade III skin toxicity was reported in 9(36%) of the patients and Grade III gastrointestinal toxicity was reported in 1 (4%) of the patients, no other grades III-IV toxicity was reported. Overall, the disease control was comparable to previous 3D-CRT studies but with much less toxicity. CONCLUSION: IMRT-based chemoradiation should be the standard of care in locally advanced carcinoma of the anal canal.

Recurrent Kimura's disease of head and neck treated with intensity-modulated radiotherapy.

Kimura's disease (KD) is a rare, chronic inflammatory disorder of unknown aetiology, which commonly affects men of the Asian race. Here, we present a case capsule of a 39- year-old man with KD of the left cheek, managed initially by surgery alone. He developed local recurrence after 6 months and was treated with steroids and isotretinoin. Eventually, steroids were discontinued due to toxicity and the lesion progressively increased in size. The patient was successfully treated using intensity-modulated radiotherapy with simultaneous integrated boost as a primary modality with minimal adverse effects. The patient has good local control and cosmetic outcome with no radiation-related toxicity at a follow-up period of 28 months.

Training for next-generation gynaecologic surgical & radiation oncologists - opportunities & challenges.

The global increase in cancer burden is a challenge for countries with scarce resources. Amongst all the malignancies, gynaecological cancer still continues to have a high incidence and prevalence leading to significant morbidity and mortality. While a multipronged strategy of decreasing the gynaecological cancer burden is a global priority, one of the key strategies to decrease the morbidity and mortality is to train gynaecological oncology specialists. Most of the developed nations have an established gynaecologic oncology training programme in the form of a well-designed curriculum and skill training. However, in developing countries where the actual disease burden of these cancers is highest, such focused training programmes have only started emerging and evolving over the past two decades. While it is a positive step to initiate such training programmes in a country like India, there are still gaps in the uniformity of curriculum and training. Also, exposure to modern practices in gynaecologic oncology surgery, chemotherapy and technology in radiation oncology, especially brachytherapy, is still insufficient in many centres. This review discusses some of the challenges and opportunities in the still evolving programmes for training gynaecologic oncologists in India.

Impact of Molecular Predictors on the Response Rates in Head and Neck Cancer Patients - an Observational Study.

Squamous cell carcinoma of head and neck region account for more than 25 % of male and more than 10 % of female cancers in India (1). Head and neck cancer treatment includes a multidisciplinary approach involving all specialties. Concurrent chemo-radiation is the standard of care in most of the subsites (2). Inspite of the multi-disciplinary approach, a plateau has been reached in terms of results with 5 year survival of locally advanced disease of around 30 % (3). In order to improve outcomes, there has been considerable interest in molecular profiling of head and neck cancers 4-10. However there is still significant paucity in terms of Indian data, hence the need for the study. The objectives are to assess the HPV-p16, EGFR and p53 status, to correlate HPV-p16, EGFR and p53 status with the response rates, to correlate HPV-p16,EGFR and p53 status with other factors like age, sex, tobacco use. Twenty five consecutive cases of histopathologically proven head and neck cancers were accrued. All patients were treated with external radiation to a dose of 66Gy in 33 fractions along with concurrent weekly cisplatin chemotherapy at a dose of 40mg/sqm. HPV-p16, EGFR and p53 mutation analysis was done on paraffin embedded histopathological blocks. PCR technique used for HPV-p16, EGFR and p53 status detection. Response assessment was done based on RECIST criteria. Correlation of HPV, EGFR and p53 status on response was done. The EGFR positivity rate was 84 %, the p53 positivity rate was 76 % and the HPV p-16 positivity rate was 28 %. Out of 25 patients, 13(52%) had complete response, 7(28 %) had partial response, 3(12 %) had stable disease and 2(8 %) had progressive disease. On correlation of molecular profile with response, there was no statistical significance between EGFR status and response (p 0.5) or HPV-p16 and response (p 0.8). However, p53 positivity was approaching significance with respect to good response (p 0.07).