Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future.

BACKGROUND: Cisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer. METHODS: A comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer. RESULTS: Randomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25-30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy. CONCLUSION: Neoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.

Impact of three-dimensional chemoradiation on pelvic bone mineral density, low back pain, and disability in cervical cancer: a prospective study.

OBJECTIVE: To prospectively analyze the effect of three-dimensional chemoradiation on the bone mineral density of pelvic bones and its association with low back pain and disability in patients with locally advanced cervical cancer. METHODS: In biopsy proven locally advanced cervical cancer patients, bone mineral density and T scores for lumbar vertebrae 5, dorsal thoracic vertebrae 12, and T scores for the femoral neck were analyzed. Low back pain was scored using the visual analog scale while disability scoring was done using the Oswestry low back pain disability scale. Furthermore, a subgroup analysis for patients (classified according to menopausal status) was performed. RESULTS: In total, 106 patients were analyzed. A statistically significant decline in mean bone mineral density was observed at all three sites (vertebrae 5 and 12, and the femoral neck) post-chemoradiation therapy compared with pretreatment bone mineral density (0.671 vs 0.828, -2.083 vs -1.531, -2.503 vs -1.626; all p<0.001). Similarly, in subgroup analyses, at all three sites, pre-menopausal patients showed a statistically significant association (0.876 vs 0.697, -1.203 vs -0.2.761, -1.403 vs -2.232; all p<0.001) while a non-significant association was observed for post-menopausal patients at vertebrae 12 (-1.707 vs -1.719; p=0.09) with a statistically significant association at vertebrae 5 and the femoral neck (0.803 vs 0.656, -1.746 vs -2.648; p<0.01). Although statistically significant low back pain and disability scores were observed overall and irrespective of menopausal status, no correlation between bone mineral density and low back pain and disability was observed. CONCLUSION: Pelvic bone mineral density decreases significantly after chemoradiation, irrespective of menopausal status. However, no correlation with low back pain and disability was observed. Pelvic bone mineral density analysis should be considered before chemoradiation in cervical cancer.

Factors Influencing the Initiation of Strong Opioids in Cancer Patients on Palliative Care: An Audit from a Tertiary Cancer Center in India.

AIM: This audit was done to analyze the factors influencing the use of strong opioids in cancer patients receiving comprehensive palliative care from a tertiary institute. MATERIALS AND METHODS: Case records of patients registered for palliative care at our center in 3 months were retrospectively reviewed and followed up throughout the course of their illness. Demographic factors, prior treatments, social support system, analgesic use at registration, and use of radiation and adjuvant analgesics were recorded. Strong opioid use and their time of initiation were evaluated, and multivariate analysis was used to identify the factors correlating with the above. RESULTS: After registration, strong opioids were initiated in 16% of the patients. It was observed that patients younger than 55 years and those with visceral metastases and history of use of weak opioids at the time of registration had a higher probability of being started on strong opioids. Factors associated with a significantly longer strong opioid-free interval were having spouse as primary caregiver, presence of skeletal metastases, use of palliative radiotherapy, and low socioeconomic status. CONCLUSION: It is certain that the use of strong opioids for adequate analgesia is a necessity for palliative-care patients. However, optimal utilization of adjunctive analgesic modalities, coupled with good supportive care, can minimize the requirement and duration of strong opioid use, especially in developing countries with limited access to specialist palliative care.

Impact of acute hematological toxicity on treatment interruptions during cranio-spinal irradiation in medulloblastoma: a tertiary care institute experience.

To analyze treatment interruptions due to acute hematological toxicity in patients of medulloblastoma receiving cranio-spinal irradiation (CSI). Prospectively collected data from case records of 52 patients of medulloblastoma treated between 2011 and 2014 was evaluated. Blood counts were monitored twice a week during CSI. Spinal irradiation was interrupted for patients with ≥grade 2 hematological toxicity and resumed after recovery to grade 1 level (TLC >3000; platelet count >75,000). Treatment interruptions and hematological toxicity were analyzed. Median age was 11 years. All patients received adjuvant CSI of 36 Gy, followed by boost of 18 Gy to posterior fossa, at 1.8 Gy per fraction. Concurrent chemotherapy was not given. Adjuvant chemotherapy was given after CSI for high risk patients. Spinal fields were interrupted in 73.1% of patients. Cause of first interruption was leucopenia in 92.1%, thrombocytopenia in 2.6%, and both in 5.3%. Median number of fractions at first interruption was 8, with 25% of interruptions in first week. Median duration for hematological recovery after nadir was 5 days for leucopenia and 3 days for thrombocytopenia. Half of the patients had at least 2 interruptions, and 19% subsequently developed grade 3 toxicity. On multivariate analysis, significant correlation with duration of delay was observed for pre-treatment haemoglobin, number of fractions at first interruption, grade and duration of recovery of leucopenia. Acute hematological toxicity with CSI is frequently under-reported. Patients with low pre-treatment hemoglobin, early onset leucopenia, profound leucopenia and prolonged recovery times are at a higher risk of having protracted courses of irradiation. Frequent monitoring of blood counts and timely interruption of spinal fields of irradiation at grade 2 level of hematological toxicity minimizes the risk of grade 3 and grade 4 toxicity, while reducing the interruptions in irradiation of the gross tumour bed.

Why Newly Diagnosed Cancer Patients Require Supportive Care? An Audit from a Regional Cancer Center in India.

PURPOSE: The present study was planned to record the distressing symptoms of newly diagnosed cancer patients and evaluate how the symptoms were addressed by the treating oncologists. MATERIALS AND METHODS: All newly diagnosed cancer patients referred to the Department of Radiotherapy during May 2014 were asked to complete a questionnaire after taking their consent. The Edmonton symptom assessment scale-regular questionnaire was used to assess the frequency and intensity of distressing symptoms. The case records of these patients were then reviewed to compare the frequency and intensity documented by the treating physician. The difference in the two sets of symptoms documented was statistically analyzed by nonparametric tests using SPSS software version 16. RESULTS: Eighty-nine patients participated in this study, of which only 19 could fill the questionnaire on their own. Anxiety was the most common symptom (97.8%) followed by depression (89.9%), tiredness (89.9%), and pain (86.5%). The treating physicians recorded pain in 83.1% whereas the other symptoms were either not documented or grossly underreported. Anxiety was documented in 3/87 patients, but depression was not documented in any. Tiredness was documented in 12/80 patients, and loss of appetite in 54/77 patients mentioning them in the questionnaire. Significant statistical correlation could be seen between the presence of pain, anxiety, depression, tiredness, and loss of appetite in the patients. CONCLUSION: The study reveals that the distressing symptoms experienced by newly diagnosed cancer patients are grossly underreported and inadequately addressed by treating oncologists. Sensitizing the oncologists and incorporating palliative care principles early in the management of cancer patients could improve their holistic care.

Assessment of usage, reuse and disposal of thermoplastic masks among radiotherapy technologists in India: A nationwide perspective.

Purpose: Radiotherapy (RT) relies on devices like thermoplastic masks (TMs), that are made up of specialized thermoplastic polymers, and used as an immobilization tool. The study aims to assess the practice of usage and reuse of TMs among radiation therapy technologists (RTTs) in India and explore their awareness of environmental impact during disposal. Materials and Methods: A cross-sectional survey was conducted among RTTs working in different healthcare settings. A structured questionnaire designed by a team of RTTs and radiation oncologists was used to collect responses. Questionnaire encompassed data pertaining to demographics, existing patient load, daily utilisation and reuse practice of TMs, preferred method of disposal and awareness of RTTs regarding environmental consequences associated with TM disposal. Results: A total of 430 RTTs participated in the study, with a median age of 31 years and a median professional experience of 8 years. Among the participants, 213 (49.6 %) reported daily TM utilization in more than 50 patients. TM reuse was reported by 350 (81.1 %) RTTs, with 257 (60 %) reusing TMs in both curative and palliative treatments. Reuse of TMs was observed more commonly in RTTs working in government facilities (81.2 %).Regarding disposal preferences, 381 (88.6%) participants preferred discarding used TMs in biomedical waste and 64.8% of these ultimately ended up as discarded scrap. Awareness regarding adverse environmental impact associated with TM disposal was reported by 320 (74.4%) participant RTTs. Conclusion: The study highlights the prevalent practice of reuse of TMs, especially in curative treatments, government-run facilities and busy treatment settings. Additionally, it emphasises the imperative for enhanced bio-medical waste management practices to facilitate more effective handling and disposal of used TMs.

"Superhero" concept to avoid anesthesia for daily radiation treatment in childhood cancer.

Advancements in therapeutic interventions have led to significant improvement in the overall management of childhood cancer. Radiotherapy forms an important component of their treatment. Modern radiotherapy technique where an optimal therapeutic ratio can be obtained demands proper and adequate immobilization of the child. This can be technically challenging sometimes, particularly when the child is noncompliant. To address this hurdle, we have used this concept of "Superhero," where we have decorated and painted the thermoplastic masks that often used in the head and neck and cranial irradiation. We have received adequate compliance for this method, and the need for anesthesia was slackened.

Nationwide Study to Assess the Psychosocial, Financial, and Professional Impact of COVID-19 Pandemic on Radiation Therapy Technologists.

PURPOSE: Radiation therapy technologists (RTTs), being the frontline health care workers, are vulnerable to COVID-19 disease and subsequent detrimental consequences of the pandemic. Hence, the study was undertaken for the comprehensive assessment of adverse effects of COVID-19 pandemic on RTTs. MATERIALS AND METHODS: This cross-sectional, survey-based study was carried out among RTTs working in various cancer centers across India. Assessment was carried out by using a questionnaire comprising the demographic profile and a structured instrument to quantify psychological, social, financial, and professional impact of COVID-19 pandemic. Responses were collected between February 1, 2021, and April 31, 2021. RESULTS: Of 302 responders, more than two third of the RTTs were concerned for getting COVID-19 disease either outside the hospital (n = 210, 69.5%) or from patients or attendants (n = 220, 72.8%). More than one third of RTTs were very much concerned for increased financial burden of COVID-19 pandemic (n = 94, 34.1%), and one third (n = 92, 30.5%) were very much concerned for newly imposed restrictions. RTTs working in a private setup (P = .000), living in a tier 1 city (P = .028), and lacking the coverage of COVID-19 disease in health insurance (P = .010) faced a significantly higher financial burden. RTTs living in tier 1 city (P = .023) and those who were in profession for > 5 years (P = .013) had significantly higher concern for ensuring proper sanitization of the professional environment. More than half (n = 171, 56.6%) were interested in taking COVID-19 vaccine. CONCLUSION: COVID-19 pandemic adversely affected psychosocial, financial, and professional well-being of RTTs even after subsidizing the initial wave, and a timely intervention is warranted for their well-being and to sustain oncologic facilities.

Brachytherapy in cervical cancer radiotherapy during COVID-19 pandemic crisis: problems and prospects.

COVID-19 pandemic has adversely affected general healthcare delivery systems and cancer care throughout the world. The management of locally advanced cervical cancer presents specific challenges in this context, especially brachytherapy and completion of radiotherapy treatment, without compromising the overall treatment time and anticipated outcomes. This article presents in detail the issues and possible solutions with currently available literature for COVID-19 and radiation, in particular brachytherapy management of locally advanced cervical cancers. The review attempts to provide possible explanations and pathways based on COVID-19 testing, brachytherapy processes including application, imaging, and fractionation, keeping in mind the overall treatment time.

Challenges of radical chemoradiation planning in Stage III non-small-cell lung cancer: Can volumetric modulated arc radiotherapy overcome an unfavourable location?

BACKGROUND AND PURPOSE: Radiotherapy treatment planning of radical doses for concurrent chemoradiation in Stage III non-small-cell lung cancer (NSCLC) presents many challenges. This dosimetric study aimed to analyse the impact of spatial location of tumour and nodal burden in limiting the achievement of normal organ constraints and the use of appropriate radiotherapy technique to address it. MATERIALS AND METHODS: Fifteen Stage III NSCLC patients underwent 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) based treatment planning. VMAT (Volumetric Modulated Arc Radiotherapy) plans were made for all patients treated by 3D-CRT (3-Dimensional Conformal Radiotherapy). A binomial logistic regression was performed to ascertain the tumour and nodal characteristics that decreased the likelihood of being planned to 60 Gy. RESULTS: Inability to achieve normal tissue constraints, particularly spinal cord dose to less than 50 Gy, during initial planning by the assigned treatment technique was the primary dose limiting factor in four patients (p = 0.02). Alternate VMAT plans could achieve the dose constraints where 3D-CRT was unsuccessful in patients with bulky central disease in two patients. This technique fell short when there was gross vertebral body erosion. CONCLUSIONS: For tumours with bulky central disease, VMAT should be preferred. With gross vertebral body erosion, even VMAT falls short if the planning target volume includes the spinal cord. In a subset of Stage III NSCLC upfront chemoradiation to radical doses may not be feasible.

Impact of volume of irradiation on survival and quality of life in glioblastoma: a prospective, phase 2, randomized comparison of RTOG and MDACC protocols.

BACKGROUND: Though conformal partial-brain irradiation is the standard adjuvant treatment for glioblastoma, there is no consensus regarding the optimal volume that needs to be irradiated. European Organisation for Research and Treatment of Cancer (EORTC) and The University of Texas MD Anderson Cancer Center (MDACC) guidelines differ from the Radiation Therapy Oncology Group (RTOG) in their approach toward peritumoral edema, whereas RTOG and MDACC guidelines differ from EORTC in the concept of boost phase. A scarcity of randomized comparisons has resulted in remarkable variance in practice among institutions. METHODS: Fifty glioblastoma patients were randomized to receive adjuvant radiotherapy using RTOG or MDACC protocols. Apart from dosimetric and volumetric analysis, acute toxicities, recurrence patterns, progression-free survival (PFS), overall survival (OS), and quality of life (QoL) were compared using appropriate statistical tests. RESULTS: Both groups were comparable with respect to demographic characteristics. Dosimetric analysis revealed significantly lower boost-phase planning treatment volumes and V60 Gy in the MDACC arm (chi-squared, P = .001 and .013, respectively). No significant differences were observed in doses with respect to organs at risk, acute toxicity, or recurrence patterns (chi-squared, P > .05). On the log-rank test, median PFS (8.8 months vs 6.1 months, P = .043) and OS (17 months vs 12 months, P = .015) were statistically superior in the MDACC group.Age, extent of resection, and proportion of whole brain receiving prescription dose were associated with improved PFS and OS on regression analysis. QoL of patients was significantly better in the MDACC group in all domains except cognitive, as assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) and Brain Cancer Module (QLQ-BN20) (general linear model, P < .05). CONCLUSIONS: Use of limited-margin MDACC protocol can potentially improve survival outcomes apart from QoL of glioblastoma patients, as compared with the RTOG protocol.

Prospective Study to Quantify Expansion Volumes Around the Involved Pelvic Lymph Nodes to Plan Simultaneous Integrated Boost in Patients With Cervical Cancer Undergoing Pelvic Intensity Modulated Radiation Therapy.

PURPOSE: This study aimed to calculate the expansion margins around enlarged pelvic lymph nodes to encompass internal motion and setup errors during intensity modulated radiation therapy with simultaneous integrated boost for cervical cancer. METHODS AND MATERIALS: Four-dimensional computed tomography scans were obtained for 19 patients with cervical cancer, and 32 fluorodeoxyglucose-avid pelvic lymph nodes were delineated in different respiratory phases to calculate respiratory displacement. Setup variations during daily treatments were estimated from on-board imaging. Descriptive statistics were used to quantify the expansion margins using Mc Kenzie and Van Herk formulas separately. An analysis of variance was used to analyze the volumetric impact of the margins. RESULTS: Based on the McKenzie formula, an internal margin (internal target volume) of 3 mm and setup margin (planning target volume) of 5 mm was required to adequately encompass respiratory and setup uncertainties, respectively. Although the use of the Van Herk formula necessitated a single 6 mm expansion margin for all uncertainties, which resulted in a significant reduction in boost volume, inherent limitations in our methodology might pose a higher risk of target miss with such smaller margins. CONCLUSIONS: An isotropic expansion margin of 3 mm for the internal target volume and 5 mm for the planning target volume is necessary for enlarged pelvic lymph nodes while planning intensity modulated radiation therapy with simultaneous integrated boost for cervical cancer.

Hurdles in radiation planning for glioblastoma: Can delayed-contrast enhanced computed tomography be a potential solution?

OBJECTIVE: Conformal radiation is the standard of care in treatment of glioblastoma. Although co-registration of magnetic resonance imaging (MRI) with early contrast enhanced computed tomography (CECT) is recommended for target delineation by consensus guidelines, ground realities in developing countries often result in availability of less-than-ideal MR sequences for treatment planning. Purpose of this study is to analyze the impact of incorporation of delayed-CECT sequences for radiation planning in glioblastomas, as an adjunct or alternative to MRI. METHODS: Case records of all patients of glioblastoma treated at our center between 2011 and 2014 were retrospectively evaluated. Gross treatment volumes were delineated on T1 contrast MRI (m-GTV), early CECT (e-GTV) and delayed CECT (d-GTV); volumetric comparisons were made using repeated measures analysis of variance and pair-wise analysis. RESULTS: Although 96% of registered patients underwent postoperative MRI, only 38% of them had desirable sequences suitable for co-registration. Median duration between acquisition of postoperative MRI and surgery was 45 days (range, 33-60), whereas that between MRI and treatment-planning CT was 5 days (range, 1-10). Statistically significant differences (P < 0.0001) were obtained between mean volumes of e-GTV (41.20cc), d-GTV (58.09cc) and m-GTV (60.52cc). Although the mean GTV increased by 46% between early CECT and MRI, the difference was only 4% between delayed CECT and MRI. CONCLUSION: Delayed CECT is superior to early CECT for co-registration with MRI for target delineation, especially when available MR sequences are less-than-ideal for treatment planning, and can be considered as the most appropriate adjunct as well as an alternative to MRI, compared to early CECT.

Acute effects of chemoradiation on cardiac function in oesophageal cancer: a MUGA scan and echo-based study.

OBJECTIVE: To study the acute effects of concurrent chemoradiation on global and regional cardiac contractility and correlate with radiation dose. METHODS: 16 patients of locally advanced oesophageal squamous cell carcinoma were serially followed up with multiple-gated acquisition (MUGA) scans and echocardiograms during the course of concurrent chemoradiation to evaluate the ejection fractions (EFs) and pericardial status, respectively. Changes in cardiac contractility were correlated with the doses received by the heart. RESULTS: Concurrent chemoradiation resulted in a significant reduction in the contractility of both left ventricle (LV) and right ventricle (RV), with a mean reduction of LVEF by 5.6% and RVEF by 6.5% over the course of treatment, which had a significant correlation with the radiation doses received by the ventricles (p=0.001). On further analysis, correlation between radiation dose and decrease in contractility was more significant in the boost phase (16 Gy in 8 fractions over one and a half weeks; p=0.001 for LV and p=0.008 for RV) compared with the initial phase (40 Gy in 20 fractions over 4 weeks; p=0.184 for LV and p=0.269 for RV). One out of 16 patients developed mild acute pericarditis. CONCLUSIONS: Concurrent chemoradiation resulted in acute decrease in EF of both ventricles in a dose-dependent manner. Correlation between cardiac doses and decrease in EF was more marked in the boost phase, suggesting a possible threshold of 40 Gy for this impairment. Nevertheless, conclusions regarding this possible threshold need to be interpreted with caution given the small sample size.