Tata Memorial Centre Evidence Based Management of Breast cancer.

ABSTRACT: The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

Translation and pilot validation of Hindi, Marathi, and Bangla translation of quality of life EORTC module (QLQ-SH-22) for assessing sexual health-related quality of life.

AIM: To translate and validate the European Organization for Research and Treatment for Cancer (EORTC) module for assessing the sexual health-related quality of life in cancer patients (QLQ-SH22), in Hindi, Marathi, and Bangla languages for clinical use. METHODS AND RESULTS: The EORTC QLQ-SH-22 was translated into Hindi, Marathi, and Bangla by adopting standard guidelines given by EORTC. Initially, the original questionnaire was forward translated by two separate translators, followed by the reconciliation of the forward translations by a third person. This was followed by two back translations of the reconciled version into English by two other translators. These back-translated questions were then compared with the original EORTC questions for accuracy, and once acceptable, a preliminary questionnaire was prepared in all three languages. These questionnaires were then pilot tested with 30 patients (10 for each language) diagnosed with any of the cancers in the pelvic region who are expected to be at risk of sexual quality of life due to tumor or treatment like pelvic radiotherapy. Participated patients had never seen or filled the questionnaire before, each patient was interviewed after filling the questionnaire for difficulty in answering, confusion, difficulty understanding, or if any of the questions were upsetting and if patients would have asked the question differently. RESULTS: None of the patients reported any changes or suggestions for all the three translations. All the translated questionnaires were well understood by all the patients. Pilot testing reports were sent to EORTC. After reviewing the entire report of Hindi, Marathi, and Bangla translations, these questionnaires were approved by the EORTC translation unit. The questionnaires are reliable with Cronbach's α for Hindi, Marathi, and Bangla being 0.69, 0.66, and 0.86, respectively. CONCLUSION: The final Hindi, Marathi, and Bangla translations of SH 22 have been approved by the EORTC and can be used to assess the sexual health of cancer patients in routine oncology practices and/or clinical studies.

CONcurrent ChEmotherapy and RadioTherapy in adjuvant treatment of breast cancer (CONCERT): a phase 2 study.

Purpose: This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer. Methods: From April 2019 to 2020, 60 patients with stage II-III invasive breast cancer planned for adjuvant taxane-based chemotherapy and radiotherapy (RT) were accrued. Local ± regional (excluding the internal mammary nodal region) RT (40 Gy in 15 fractions ± boost) was started with the third cycle of an adjuvant taxane in a 3-weekly schedule or with the eighth cycle in a weekly schedule. Results: Thirty-six patients received 3-weekly paclitaxel regimen and 24 received weekly paclitaxel regimen. The commonly used technique was three-dimensional conformal RT which was employed in 58% of patients. Regional RT, including the medial supraclavicular region, was done in 42 patients (70%). No dose-limiting (grade 3 or 4) toxicity was documented and all patients completed CTRT without any treatment interruption. The median ejection fraction pre and post CTRT 6 months was 60% (p = 0.177). The median value of cardiac enzyme (Troponin T ng/L) decreased from 37 to 20 (p = 0.009) post CTRT 6 months. Of the 54 patients who underwent the pulmonary function tests, there was no significant difference in various parameters like functional vital capacity (FVC) (2.29 versus 2.2 L, p = 0.375), forced expiratory volume at 1 second (FEV1) (1.86; 1.82; p = 0.365), FEV1/FVC (81.5; 81.43; p = 0.9) and diffusion lung capacity for carbon monoxide (88.3; 87.6; p = 0.62). At a median follow-up of 34 months, the 3-year actuarial rate of disease-free survival and overall survival was 75% and 98.3%, respectively. Quality of life scores (QOL) improved after treatment for most of the domains comparable to the pre-RT scores. Conclusion: Taxane-based adjuvant CTRT is a safe option and results in minimal toxicity and excellent compliance. It has favourable impact on cardio-pulmonary profile and QOL scores.

Can knowledge based treatment planning of VMAT for post-mastectomy locoregional radiotherapy involving internal mammary chain and supraclavicular fossa improve performance efficiency?

Introduction: To validate and evaluate the performance of knowledge-based treatment planning for Volumetric Modulated Arc Radiotherapy for post-mastectomy loco-regional radiotherapy. Material and methods: Two knowledge-based planning (KBP) models for different dose prescriptions were built using the Eclipse RapidPlanTM v 16.1 (Varian Medical Systems, Palo Alto, USA) utilising the plans of previously treated patients with left-sided breast cancer who had undergone irradiation of the left chest wall, internal mammary nodal (IMN) region and supra-clavicular fossa (SCF). Plans of 60 and 73 patients were used to generate the KBP models for the prescriptions of 40 Gy in 15 fractions and 26 Gy in 5 fractions, respectively. A blinded review of all the clinical plans (CLI) and KBPs was done by two experienced radiation oncology consultants. Statistical analysis of the two groups was also done using the standard two-tailed paired t-test or Wilcoxon signed rank test, and p<0.05 was considered significant. Results: A total of 20 metrics were compared. The KBPs were found to be either better (6/20) or comparable (10/20) to the CLIs for both the regimens. Dose to heart, contralateral breast,contralateral lung were either better or comparable in the KBP plans except of ipsilateral lung. Mean dose (Gy) for the ipsilateral lung are significantly (p˂0.001) higher in KBP though the values were acceptable clinically. Plans were of similar quality as per the result of the blinded review which was conducted by slice-by-slice evaluation of dose distribution for target coverage, overdose volume and dose to the OARs. However, it was also observed that treatment times in terms of monitoring units (MUs) and complexity indices are more in CLIs as compared with KBPs (p<0.001). Discussion: KBP models for left-sided post-mastectomy loco-regional radiotherapy were developed and validated for clinical use. These models improved the efficiency of treatment delivery as well as work flow for VMAT planning involving both moderately hypo fractionated and ultra-hypo fractionated radiotherapy regimens.

Using Artificial Intelligence for Optimization of the Processes and Resource Utilization in Radiotherapy.

The radiotherapy (RT) process from planning to treatment delivery is a multistep, complex operation involving numerous levels of human-machine interaction and requiring high precision. These steps are labor-intensive and time-consuming and require meticulous coordination between professionals with diverse expertise. We reviewed and summarized the current status and prospects of artificial intelligence and machine learning relevant to the various steps in RT treatment planning and delivery workflow specifically in low- and middle-income countries (LMICs). We also searched the PubMed database using the search terms (Artificial Intelligence OR Machine Learning OR Deep Learning OR Automation OR knowledge-based planning AND Radiotherapy) AND (list of Low- and Middle-Income Countries as defined by the World Bank at the time of writing this review). The search yielded a total of 90 results, of which results with first authors from the LMICs were chosen. The reference lists of retrieved articles were also reviewed to search for more studies. No language restrictions were imposed. A total of 20 research items with unique study objectives conducted with the aim of enhancing RT processes were examined in detail. Artificial intelligence and machine learning can improve the overall efficiency of RT processes by reducing human intervention, aiding decision making, and efficiently executing lengthy, repetitive tasks. This improvement could permit the radiation oncologist to redistribute resources and focus on responsibilities such as patient counseling, education, and research, especially in resource-constrained LMICs.

Modified Houdek vault applicator for high-dose-rate brachytherapy: a technical report and case series.

PURPOSE: Treatment of isolated post-surgical vault recurrence of cervical and endometrial cancers in previously unirradiated patients includes external beam radiotherapy (EBRT) ± concomitant chemotherapy, followed by brachytherapy (BT) boost. Supra-vaginal component of vault disease often requires interstitial BT for optimal dose coverage. We describe technical details and preliminary case series using modified Houdek vault applicator (MHVA) developed at our institution for limited intra-cavitary plus interstitial high-dose-rate (HDR) vault BT. MATERIAL AND METHODS: Nineteen patients with vaginal vault recurrences received BT boost with MHVA between October 2015 and May 2018. All underwent BT application and CT-based BT planning after completion of EBRT ± concomitant chemotherapy. RESULTS: Median EQD2 of BT dose in patients with carcinoma cervix recurrence (n = 15, α/ß = 10) was 18.8 Gy, and in those with endometrial cancer recurrence was 22.08 Gy (n = 4, α/ß = 4.5). Median total EQD2 was 68.8 Gy and 72.08 Gy, respectively. Mean 2 cc of bladder, rectum, and sigmoid EBRT + BT doses (EQD2, α/ß = 3) were 65.38 Gy (±7.76), 63.37 Gy (±5.52), and 57.04 Gy (±4.45), respectively. At 6-8 weeks, 17 patients showed complete response (CR). With median follow-up of 20.5 months, 2-year overall survival was 95% (95% CI: 85.2-100.0%), and 2-year progression-free survival was 79.4% (95% CI: 61.0-97.8%). Late toxicities seen were grade 2 proctitis in 1 patient, grade 1 proctitis in 5, grade 2 urethritis in 1, grade 3 cystitis in 1, and recto-vaginal fistula in 1 patient (with disease controlled). Recurrence rate was 6.7 times higher in patients with post-EBRT disease greater than 10 mm (p = 0.01). CONCLUSIONS: MHVA is a simple solution for intra-cavitary and interstitial HDR-BT boost in isolated vault cancers post-surgery, achieving acceptable dosimetric parameters. Preliminary clinical outcomes and late toxicities are satisfactory.

Defining dose constraints for catheter insertion sites to minimize toxicity after interstitial breast brachytherapy.

PURPOSE: The purpose of this study was to define dose constraints for catheter insertion sites to minimize probability of prominent post-therapy skin marks after interstitial breast brachytherapy. METHODS AND MATERIALS: Forty patients who had undergone interstitial breast brachytherapy were studied at followup at least 2 years after the procedure. Their implant marks were compared with background skin and areola and scored as Gr0 = invisible (same color as surrounding skin), Gr1 = darker than surrounding skin but lighter than areola or hypopigmentation, and Gr2 = same color as areola or darker. Highest point doses received in each plane of implant and their corresponding closest distances from clinical target volume, 85% isodose, and closest catheter dwell point were used for analysis. A logistic regression was performed to ascertain effects of various dosimetric parameters on the probability of Gr2 marks. Receiver operating characteristic curve was generated to derive cutoffs. RESULTS: A total of 280 dose points were studied. Median values for various parameters were 1.4 Gy (0.24-3.74) for Dose max and 1.6 cm, 1.5 cm, and 1.0 cm for Dist CTV min, Dist Iso min, and Dist Dwell min, respectively. On logistic regression, increasing Dose max alone was associated with an increased likelihood of developing Gr2 marks. Each unit increase of Dose max increased probability of development of Gr2 skin marks by 5.0% (2.391-10.328). Receiver operating characteristic analysis also showed greatest odd ratio (8.0), sensitivity (74.8%), and specificity (73%) for Dose max. CONCLUSIONS: It seems prudent to restrict dose to catheter insertion sites for better cosmesis.