The modern landscape of radiotherapy in thyroid malignancies.

Thyroid carcinoma is the most common malignancy of the endocrine system and accounts for nearly 1.5% of all new cancer cases in India. The incidence of thyroid cancers is on the rise secondary to multiple factors including the widespread use of radiological imaging. Surgery remains the cornerstone of treatment, and radioactive iodine therapy plays a pivotal role in differentiated thyroid cancer. Radiation therapy appears to be an underutilized treatment modality. In this review, we have summarized the role of radiation in the treatment of thyroid cancer.

Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, the number of eligible patients benefiting from high-precision particle therapy technology is projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

Evaluation of doses to pelvic lymph node regions from image-guided high-dose-rate interstitial brachytherapy for carcinoma of the uterine cervix.

Purpose: Interstitial brachytherapy (ISBT) is indicated for intact cervical carcinoma (IN-CC) if intracavitary brachytherapy (ICRT) is not feasible and also in vault carcinoma (VA-C). We aimed to evaluate the doses to pelvic lymph node regions in IN-CC and VA-C treated with ISBT. Material and methods: Ten patients (6 IN-CC, 4 VA-C) were chosen for this dosimetric study. IN-CC had a central tandem in addition to the needles. External iliac (EI-N), internal iliac (II-N), obturator (OB-N) and sacral (SA-N) groups of lymph nodes were delineated. A dose of 10 grays (Gy) and 8 Gy each × 2 fractions was prescribed to the target in IN-CC and VA-C respectively. Doses received by 100%, 90% and 50% volume (D100, D90, D50) and D2cc, D1cc, D0.1cc were evaluated. Doses to lymph nodal groups in IN-CC vs. VA-C were compared using Student's t-test. Results: For 20 implants, the median number of needles was 18 (range, 16-20). Mean D90 and D2cc of the combined bilateral OB-N, II-N, EI-N and SA-N groups were 33.62 ±3.46% and 102.94 ±10.71%, 6.98 ±0.65% and 39.69 ±3.64%, 5.1 ±0.51% and 15.4 ±0.8%, 7.76 ±0.95% and 15.36 ±1.09% of the prescribed doses respectively. Patients with a central tandem (IN-CC) received significantly higher doses to external, internal iliac and sacral group of lymph nodes (p < 0.001) as compared to VA-C. Conclusions: In patients with cervical carcinoma treated with ISBT, pelvic lymph node groups received significant doses. The dose contribution to pelvic lymph nodes is higher in patients with intact cervical cancer where a central tandem is used as compared to post-operative patients.

The American Brachytherapy Society and Indian Brachytherapy Society consensus statement for the establishment of high-dose-rate brachytherapy programs for gynecological malignancies in low- and middle-income countries.

PURPOSE: The global cervical cancer burden is disproportionately high in low- and middle-income countries (LMICs), and outcomes can be governed by the accessibility of appropriate screening and treatment. High-dose-rate (HDR) brachytherapy plays a central role in cervical cancer treatment, improving local control and overall survival. The American Brachytherapy Society (ABS) and Indian Brachytherapy Society (IBS) collaborated to provide this succinct consensus statement guiding the establishment of brachytherapy programs for gynecological malignancies in resource-limited settings. METHODS AND MATERIALS: ABS and IBS members with expertise in brachytherapy formulated this consensus statement based on their collective clinical experience in LMICs with varying levels of resources. RESULTS: The ABS and IBS strongly encourage the establishment of HDR brachytherapy programs for the treatment of gynecological malignancies. With the consideration of resource variability in LMICs, we present 15 minimum component requirements for the establishment of such programs. Guidance on these components, including discussion of what is considered to be essential and what is considered to be optimal, is provided. CONCLUSIONS: This ABS/IBS consensus statement can guide the successful and safe establishment of HDR brachytherapy programs for gynecological malignancies in LMICs with varying levels of resources.

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.

Factors affecting the incorporation of extracorporeally irradiated autograft for the treatment of bone tumours-a retrospective analysis from a tertiary referral centre.

PURPOSE: Re-implantation of the tumor bearing autograft following extracorporeal radiation therapy (ECRT) has been established as an oncologically safe biological reconstruction technique following resection of bone sarcomas. However, factors affecting the ECRT graft-host bone incorporation have not been fully investigated. An insight into the factors that influence graft incorporation can circumvent the complications and increase graft survival. METHODS: A total of 96 osteotomies in 48 patients with intercalary resections of primary extremity bone sarcomas (mean age 15.8 years, mean follow-up 42.1 months) were analyzed retrospectively for factors ECRT autograft-host bone union. RESULTS: On univariate analysis, age < 20 years, metaphyseal osteotomy site, V-shaped diaphyseal osteotomy, and use of additional plate at diaphyseal osteotomy had a significantly faster time to union, while gender, tumour type, bone involved, resection length, chemotherapy, type of fixation, and use of intra-medullary fibula did not influence union time. In multivariate analysis, V-shaped diaphyseal osteotomy and use of additional plate at diaphyseal ostetomy were the independent factors with favourable time to union. None of the analyzed factors was found to have a significant effect on the union rate. The major complications were non-union in 11.4% patients, graft failure in 2.1%, infection in 12.5%, and soft tissue local recurrences in 14.5% patients. CONCLUSION: Modified diaphyseal osteotomy and augmentation of the stability of the reconstruction using additional small plates enhance the incorporation of ECRT autograft.

Determinants and impact of diagnostic interval in bone sarcomas: A retrospective cohort study.

BACKGROUND: Diagnostic delays in cancers are frequent in developing countries due to poor health infrastructure. Existing literature from developed countries suggests that diagnostic interval in bone sarcomas is primarily dictated by tumour biology with no impact on survival. This study evaluates the social and biological determinants of the diagnostic interval in bone sarcomas in a resource-challenged setting and assesses its impact on treatment outcomes. METHODS: A retrospective single-institutional study was conducted on patients with high-grade bone sarcomas recorded in the sarcoma clinic database between 2003 and 2018. Baseline clinical characteristics and treatment outcomes were recorded. Logistic regression was performed to assess the impact of baseline clinical and social characteristics (distance from treating centre and rural vs. urban residence) on the diagnostic interval. Further, the impact of diagnostic interval on histologic response to neoadjuvant chemotherapy, amputation requirement in extremity sarcomas and survival was evaluated. RESULTS: A total of 1227 patients were included for analysis. The median diagnostic interval was 4 months (3-7 months). Age above 18 years, Ewing sarcoma (ES) diagnosis, absence of fever at presentation and tumour size above 7.5 cm were predictors of a longer diagnostic interval (>4 months). The length of the diagnostic interval did not impact amputation requirement or survival outcomes. However, the proportion of patients with good necrosis post-neoadjuvant chemotherapy was lower among patients with longer diagnostic intervals (25% vs. 34·16%; p-value = .04). CONCLUSION: Tumour characteristics rather than social factors determined the diagnostic interval. Diagnostic interval did not impact survival outcomes even in a resource-constrained setting.

Oligometastatic breast cancer: An institutional analysis.

Introduction: Oligometastatic represents a distinctive subset of metastatic breast cancer (MBC). Incidence has been reported, in 1-5% of all newly diagnosed MBC. Literature is very sparse, especially from India. Material and Methods: We have ambispectively screened 500 patients of upfront female MBC between the period of January 2013 and August 2018 at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi and 120 patients of oligometastatic breast cancer (OMBC) were included for analysis. Clinical, pathological, receptor status (ER estrogen receptor, PR progesterone receptor, and HER2/neu human epidermal growth factor), radiological, treatment, and survival details were recorded. Results: The median age of presentation was 50 (range 22-78) years. One organ was involved in 96 (80%) patients, and two organs were involved in 36 (20%) patients. ER and/or PR was positive in 48 (40.0%), ER/PR, and HER2/neu were positive in 28 (23.3%) cases. Only HER2/neu was positive in 21 (17.5%), and triple negativity was seen in 23 (19.2%) patients. Ninety-four (78.3%) patients received neoadjuvant therapy, and 12 (10%) patients underwent conservative breast surgery. The overall response rate at the metastatic site was 74.1%, and a complete response was seen in 42.5% of patients. Median progression-free survival (PFS) for the cohort was 25.43 months. The estimated PFS at 2 years and, at 5 years, was 54.6% and 21.6%, respectively. The hormone receptor positivity, bone metastasis, and patients with surgery after neoadjuvant chemotherapy (NACT) had a statistically significant better PFS on multivariate analysis. In a subset analysis of HER2/neu receptor-positive patients, who received targeted therapy showed better PFS compared to those who did not receive. Conclusion: The incidence of OMBC is 24% of the total MBC. The patients with OMBC who have hormone receptor-positive, bone-only metastasis, and surgery after NACT show a better outcome.

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis.

IMPORTANCE: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial. METHODS: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes. RESULTS: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm. CONCLUSION: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.

Development and validation of a prognostic score at baseline diagnosis for Ewing sarcoma family of tumors: a retrospective single institution analysis of 860 patients.

INTRODUCTION: Prognostic scores in Ewing sarcoma including baseline clinical and laboratory characteristics are necessary for pre-treatment risk stratification. In this study, we formulated and validated a prognostic model for baseline risk categorization in Ewing sarcoma. MATERIALS AND METHODS: A retrospective single-institutional study was conducted on Ewing sarcoma patients treated uniformly between January 2003 and December 2018. Baseline clinical/pathological characteristics and survival outcomes were noted from medical records. The cohort was randomised into a derivation and validation cohort. A prognostic score was formulated by including independent prognostic factors from the derivation cohort by multivariable analysis. The prognostic model was validated in the validation cohort along with estimation of its predictive ability. RESULTS: A total of 860 patients were included with 40.3% having baseline metastases. Tumor diameter >5 cm (HR 2.04; P<0.001; score 2), baseline metastases (HR 2.33; P<0.001, score 2), and total leucocyte count >11000/mm3 (HR 1.44; P=0.015; score 1) were independent predictors of overall survival in derivation cohort and included for prognostic score calculation. Patients were categorized into low (score 0), intermediate (score 1-3) and high-risk (score 4-5) groups. Harrell's c-indexes of the model were 0.625, 0.622 and 0.624 in the derivation, validation and whole cohort respectively. The timed AUC of ROC of the prognostic score-group for 5-year survival was 0.72, 0.71 and 0.73 in the derivation, validation and whole cohort respectively. CONCLUSIONS: We have formulated and validated a prognostic score for Ewing sarcoma incorporating baseline clinical and laboratory parameters, with fair predictive ability for risk stratification and facilitating risk-adapted personalized therapy.

Adjuvant treatment in cervical, vaginal and vulvar cancer.

Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.

Cancer of the cervix uteri: 2021 update.

Since the publication of the 2018 FIGO Cancer Report, giant strides have been made in the global effort to reduce the burden of cervical cancer, with the World Health Organization (WHO) rolling out a global strategy for cervical cancer elimination, aiming for implementation by 2030. In over 130 countries, including low- and middle-income countries, HPV vaccination is now included in the national program. Screening has seen major advances with wider implementation of HPV testing. These interventions will take a few years to show their impact. Meanwhile, over half a million new cases are added each year. FIGO's revised staging of cervical cancer (2018) has been widely implemented and retrospective analyses of data based on the new staging have been published. Minimally invasive surgery has been shown to be disadvantageous in women with cervical cancer. This chapter discusses the management of cervical cancer based on the stage of disease, including attention to palliation and quality of life issues.

Low-dose radiation therapy for COVID-19 pneumonia: a pilot study.

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.

Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.

Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy.

INTRODUCTION: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. PATIENTS AND METHODS: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. CONCLUSION: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk.

Cancer of the cervix uteri.

Since the publication of the last FIGO Cancer Report there have been giant strides in the global effort to reduce the burden of cervical cancer, with WHO announcing a call for elimination. In over 80 countries, including LMICs, HPV vaccination is now included in the national program. Screening has also seen major advances with implementation of HPV testing on a larger scale. However, these interventions will take a few years to show their impact. Meanwhile, over half a million new cases are added each year. Recent developments in imaging and increased use of minimally invasive surgery have changed the paradigm for management of these cases. The FIGO Gynecologic Oncology Committee has revised the staging system based on these advances. This chapter discusses the management of cervical cancer based on the stage of disease, including attention to palliation and quality of life issues.