Feasibility and safety of shortened hypofractionated high-dose palliative lung radiotherapy - A retrospective planning study.

OBJECTIVE: Assess the safety and feasibility of shortened hypofractionated high-dose palliative lung radiotherapy in a retrospective planning study. METHODS: Fifteen late stage (III or IV) NSCLC lung radiotherapy patients previously treated with the standard palliative 36 Gy in 12 fractions (12F) schedule were non-randomly selected to achieve a representative distribution of tumour sizes, volumes, and location. Plans were produced using 30 Gy in 5 fractions (5F) and 6 fractions (6F) using a 6MV FFF co-planar VMAT technique. Plans were optimised to meet dose-constraints for planning target volumes (PTVs) and organs at risk (OARs) with established OAR constraints expressed as biological equivalent doses (BEDs). The potential safety was assessed using these BEDs and also with reductions of 10% (BED-10%) and 20% (BED-20%) to account for a reduction in tolerance doses from the effects of chemotherapy or surgery. RESULTS: Mandatory BED constraints were met for all fifteen 5F and 6F plans; BED-10% constraints were met by all 6F plans and six 5F plans. BED-20% constraints were met by six 6F and three 5F respectively. CONCLUSION: It is potentially safe and feasible to deliver high-dose palliative radiotherapy for late stage NSCLC using the 5F or 6F regimes described, when planned to comparable OAR BEDs as standard radical techniques. It appears toxicity from these regimes should be within acceptable limits provided the dose-constraints described are met. A Phase II study is required to fully assess safety and feasibility, the outcomes of which could reduce the number of patient hospital visits for radiotherapy, thereby benefiting patients and optimising resource utilisation.

Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience.

CONTEXT: Stereotactic body radiotherapy (SBRT) is increasingly being used for early-stage lung cancer and lung oligometastases. AIMS: To report our experience of setting up lung SBRT and early clinical outcomes. SETTINGS AND DESIGN: This was a retrospective, interventional, cohort study. SUBJECTS AND METHODS: Patients were identified from multidisciplinary tumor board meetings. They underwent four-dimensional computed tomography-based planning. The ROSEL trial protocol, the Radiation Therapy Oncology Group (RTOG) 0236, and the UK-Stereotactic Ablative Body Radiotherapy Consortium guidelines were used for target volume and organs-at-risks (OARs) delineation, dosimetry, and plan quality assessment. Each SBRT plan underwent patient-specific quality assurance (QA). Daily online image guidance using KVCT or MVCT was done to ensure accurate treatment delivery. STATISTICAL ANALYSIS USED: Microsoft Excel 2010 was used for data analysis. RESULTS: Fifteen patients were treated to one or more lung tumors. One patient received helical tomotherapy in view of bilateral lung oligometastases at similar axial levels. All the remaining patients received volumetric modulated arc therapy (VMAT)-based treatment. The prescription dose varied from 40 to 60 Gy in 5-8 fractions with alternate-day treatment. The mean and median lung V20 was 5.24% and 5.16%, respectively (range, 1.66%-9.10%). The mean and median conformity indexes were 1.02 and 1.06, respectively (range, 0.70-1.18). After a median follow-up of 17 months, the locoregional control rate was 93.3%. CONCLUSIONS: SBRT was implemented using careful evaluation of OAR dose constraints, dosimetric accuracy and plan quality, patient-specific QA, and online image guidance for accurate treatment delivery. It was safe and effective for early-stage nonsmall cell lung cancer and lung metastases. Prospective data were collected to audit our outcomes.

Next generation sequencing in lung cancer: An initial experience from India.

INTRODUCTION: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients. MATERIAL AND METHOD: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform. RESULTS: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%). CONCLUSION: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.

Indian Council of Medical Research consensus document on hepatocellular carcinoma.

This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.

How do clinicians rate patient's performance status using the ECOG performance scale? A mixed-methods exploration of variability in decision-making in oncology.

BACKGROUND: Medical decisions made by oncology clinicians have serious implications, even when made collaboratively with the patient. Clinicians often use the Eastern Clinical Oncology Group (ECOG) performance status (PS) scores to help them make treatment-related decisions. METHODS: The current study explores the variability of the ECOG score when applied to 12 predetermined specially designed clinical case vignettes presented to a group of oncology clinicians (n = 72). The quantitative analysis included evaluation of variability of ECOG PS scores and exploration of rater and patient-related factors which may influence the final ECOG rating. In-depth interviews were conducted with oncology clinicians to ascertain factors that they felt were important while making treatment-related decisions. Basic and global themes were generated following qualitative data analysis. RESULTS: Quantitative results showed that there was poor agreement in ECOG rating between raters. Overall concordance with the gold standard rating ranged between 19.4% and 56.9% for the vignettes. Moreover, patients deemed to have socially desirable qualities (p < 0.004) were rated to have better PS and women patients (p < 0.004) to have worse PS. Clinicians having international work experience had increased concordance with ECOG PS rating. Qualitative results showed that 'perceived socio-economic background of the patient', 'age of the patient', 'patient's and family's preferences' and 'past treatment response' were the major themes highlighted by respondents that influenced the treatment-related decisions made by clinicians. CONCLUSION: There is considerable variability in ECOG PS determined by clinicians. Decision-making in oncology is complex, multifactorial and is influenced by rater and patient-related factors.

Development and validation of a decision support tool to select IMRT as radiotherapy treatment planning modality for patients with locoregionally advanced non-small cell lung cancers (NSCLC).

OBJECTIVE:: Radiation planning for locally-advanced non-small cell lung cancer (NSCLC) can be time-consuming and iterative. Many cases cannot be planned satisfactorily using multisegment three-dimensional conformal radiotherapy (3DCRT). We sought to develop and validate a predictive model which could estimate the probability that acceptable target volume coverage would need intensity modulated radiotherapy (IMRT). METHODS:: Variables related to the planning target volume (PTV) and topography were identified heuristically. These included the PTV, it's craniocaudal extent, the ratio of PTV to total lung volume, distance of the centroid of the PTV from the spinal canal, and the extent PTV crossed the midline. Metrics were chosen such that they could be measured objectively, quickly and reproducibly. A logistic regression model was trained and validated on 202 patients with NSCLC. A group of patients who had both complex 3DCRT and IMRT planned was then used to derive the utility of the use of such a model in the clinic based on the time taken for planning such complex 3DCRT. RESULTS:: Of the 202 patients, 93 received IMRT, as they had larger volumes crossing midline. The final model showed a good rank discrimination (Harrell's C-index 0.84) and low calibration error (mean absolute error of 0.014). Predictive accuracy in an external dataset was 92%. The final model was presented as a nomogram. Using this model, the dosimetrist can save a median planning time of 168 min per case. CONCLUSION:: We developed and validated a data-driven, decision aid which can reproducibly determine the best planning technique for locally-advanced NSCLC. ADVANCES IN KNOWLEDGE:: Our validated, data-driven decision aid can help the planner to determine the need for IMRT in locally advanced NSCLC saving significant planning time in the process.

Impact of modern radiotherapy techniques on survival outcomes for unselected patients with large volume non-small cell lung cancer.

OBJECTIVE:: Intensity modulated radiotherapy (IMRT) is used, where necessary, for bulky or complex-shaped, locally advanced, non-small cell lung cancer (NSCLC). We evaluate our real-world experience with radical radiotherapy including concurrent chemoradiation (CCRT), and analyse the impact of IMRT on survival outcomes in patients with larger volume disease. METHODS:: All patients treated between May 2011 and December 2017 were included. Analyses were conducted for factors affecting survival, including large volume disease that was defined as planning target volume (PTV) > 500 cc. RESULTS:: In 184 patients with large volume disease, the median overall survival was 19.2 months, compared to 22 months seen with the overall cohort of 251 patients who received radical radiotherapy. PTV and using CCRT were significant predictors for survival. IMRT was used in 93 (50.5%) of 184 patients with large PTV. The patients treated using IMRT had significantly larger disease volume (median PTV = 859 vs 716 cc; p-value = 0.009) and more advanced stage (proportion of Stage IIIB: 56 vs 29%; p-value = 0.003) compared to patients treated with three-dimensional conformal radiotherapy. Yet, the outcomes with IMRT were non-inferior to those treated with 3DCRT. CCRT was used in 103 (56%) patients with large volume disease and resulted in a significantly better median survival of 24.9 months. The proportional benefit from CCRT was also greater than in the overall cohort. CONCLUSION:: Despite being used for larger volume and more advanced NSCLC, inverse-planned IMRT resulted in non-inferior survival. ADVANCES IN KNOWLEDGE:: IMRT enables the safe use of curative CCRT for large-volume, locally-advanced NSCLC.

Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiation therapy for left sided breast cancer patients: A prospective service development analysis.

INTRODUCTION: Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers. METHODS AND MATERIALS: Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose. RESULTS: The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product. CONCLUSION: Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

Radical radiotherapy or chemoradiotherapy for inoperable, locally advanced, non-small cell lung cancer: Analysis of patient profile, treatment approaches, and outcomes for 213 patients at a tertiary cancer center.

INTRODUCTION: Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016. RESULTS: RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27-88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P < 0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P < 0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment. CONCLUSION: RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy.

AIMS: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. METHODS: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65Gy/25Fr/5 weeks (n = 18), or 60Gy/20Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. RESULTS: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2 genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2Gy equivalent doses (EQD2) to the rectum and bladder (α/ß = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher VEQD2-60Gy (13.2 vs 9.9cc, p = 0.007) and VEQD2-50Gy (20.6 vs 15.4cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher VEQD2-70Gy (30.4 vs 18.4cc, p = 0.001) and VEQD2-65Gy (44.0 vs 28.8cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for VEQD2-60Gy was 9.7cc and for VEQD2-50Gy was 15.9cc. For grade 2 GU symptoms, the threshold values were 23.6cc for VEQD2-70Gy and 38.1cc for VEQD2-65Gy. CONCLUSIONS: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.

Serpin b3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer.

INTRODUCTION: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3. METHODS: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1. RESULTS: Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95% confidence interval. 1.14-3.10; p = 0.002). CONCLUSIONS: SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.

Malignant struma ovarii: the west of Scotland experience and review of literature with focus on postoperative management.

INTRODUCTION: Malignant struma ovarii is an extremely rare ovarian tumour containing malignant thyroid carcinoma within differentiated thyroid tissue, as the predominant tissue type. Surgery for suspected ovarian tumour and incidental pathological diagnosis is the most common presentation. Evidence supporting any particular approach to the clinical management of this condition is limited, mainly consisting of case reports, small series or pathological case series. There is no randomised evidence for postoperative management in view of the rarity of this condition. The opinion is divided between conservative management versus total thyroidectomy and radio-iodine ablation. METHODS: We carried out a retrospective review of our series with focus on postoperative management of this rare condition. A review of existing literature was also carried out. RESULTS: Six patients with a median age of 52 years presented with various symptoms of abdominal pain, pressure or menstrual problems. After the initial gynaecological resection and specialised pathology review, they were subsequently treated with total thyroidectomy and administration of radioactive iodine. All of these six patients are in remission at a median follow up of 60 months. CONCLUSION: We favour aggressive postoperative management with total thyroidectomy and radioactive iodine, and long-term follow up of these patients.

Image-guided vulvovaginal interstitial brachytherapy in the treatment of primary and recurrent gynecological malignancies.

PURPOSE: Evaluation of interstitial high-dose-rate brachytherapy (HDRB) to the vulvovaginal region both alone and in combination with external beam radiotherapy (EBRT) for primary or recurrent gynecological malignancy. METHODS AND MATERIALS: From 1998 to 2009, 37 women with a mean age of 68 years were treated with transperineal interstitial HDRB. Fifteen patients (40.5%) were treated for primary disease, whereas 22 (59.5%) patients were treated for recurrent disease. Median time to local recurrence was 31 months (2-312 months). Primary sites included endometrium (12), vulva (11), vagina (10), vulvovagina (1), cervix (1), and bladder (2). Thirty-one patients (83.7%) in this series were treated with radical intent, whereas 6 (16.3%) were treated with palliative intent. Radically treated patients received between 45 and 60Gy (median, 45Gy) of EBRT. The median number of days from EBRT to HDR boost was 5 days (1-35 days). The HDRB doses ranged from 11Gy in two fractions to 42Gy in six fractions (dose per fraction varied from 4 to 8.5Gy) and fractions were given at least 6-8h apart. RESULTS: Eight of the 31 patients (26%) treated with radical intent relapsed locally. Eleven of 37 patients (30%) treated with either radical or palliative intent recurred locally. The 2- and 5-year local progression-free survival was 74% and 63.4%, respectively. The total progression-free survival, which includes local, locoregional/nodal, and distant recurrence, at 2 and 5 years, was 73.6% and 45.6%, respectively. With a mean follow-up of 27 months (3.8-111.9 months), the median survival for the patient group was 16.6 months with a 2- and 5-year overall survival of 47.7% and 36.4%, respectively. Acute Grade 3 toxicity was seen in 13 (35%) of the 37 patients (skin: 10, urinary: 2, genital: 2, gastrointestinal: 0). No acute Grade 4 toxicities were seen. A total of 10 of the 37 patients (27%) developed late Grade 3 toxicities. Five of the 22 patients (22%) treated for recurrent disease with radical intent developed Grade 3 toxicity (skin: 4, urinary: 2, genital: 1, radiation-induced fracture of acetabulum: 1, and gastrointestinal: 0), whereas 1 of the 6 patients treated with palliative intent had Grade 3 toxicity affecting skin. No late Grade 4 toxicities were seen. CONCLUSION: This retrospective series suggests that interstitial perineal HDRB is a safe and effective treatment option for primary or locally recurrent gynecological malignancies. It is a valuable option in patients who have received previous EBRT to the pelvis, achieving good local control with acceptable late treatment-related side effects.

Dose-dense and dose-intense chemotherapy for small cell ovarian cancer: 2 cases and review of literature.

Small cell carcinomas of the ovary (SCCO) are rare and aggressive malignant neoplasms carrying a poor prognosis. Although multi-modality treatment including chemotherapy leads to a high initial response rate, the majority of these patients relapse quickly and die within 2 years of diagnosis. Because these tumours are rare, there is no consensus to support any particular approach to management. We present 2 cases and review the relevant literature to make a number of recommendations. The treatment of these unusual cases should to be individually discussed in a multi-disciplinary team and multi-modality treatment including surgery, chemotherapy and radiotherapy should be considered for patients with limited disease. Conservative, fertility-preserving surgery may be considered in younger women with early-stage disease. Induction chemotherapy with weekly dose-dense and dose-intense carboplatin and taxane is useful. Prophylactic cranial irradiation (PCI) may be considered in patients in remission after primary treatment with chemotherapy or surgery.

Positron emission tomography with computed tomography (PET-CT) to evaluate the response of bone metastases to non-surgical treatment.

A case of solitary bone metastasis from breast cancer, where MRI assessment of treatment response was inaccurate and whole-body fluorodeoxyglucose ((18)FDG) positron emission tomography with computed tomography (PET-CT) proved more reliable and objective, is presented.

Sonographically guided core biopsy in the assessment of thyroid nodules.

PURPOSE: This study was conducted to assess the value of sonographically guided core biopsy in the evaluation of thyroid nodules by comparison with fine-needle aspiration cytology (FNAC) performed with and without sonographic guidance. METHODS: We performed a retrospective analysis of a consecutive series of 645 thyroid samples obtained at a single center. Samples came from 422 patients who underwent FNAC (with or without sonographic guidance), sonographically guided core biopsy, or excision of thyroid tissue with or without prior frozen sectioning. Final diagnoses were obtained from surgery or clinical follow-up. Initial and final diagnoses were compared. RESULTS: Adequate samples for assessment were obtained in 87% of core biopsies, compared with 60% of cytology aspirates (p <0.001). Sonographically guided core biopsy and sonographically guided FNAC both had zero false-negative rates for the diagnosis of malignancy, compared with a 7.0% false-negative rate (95% confidence interval, 2.0-12.0%) for aspiration cytology when sonography was not used. With core biopsy, 11% of patients required surgical confirmation of the diagnosis, compared with 43% of patients following FNAC (p <0.001). There were no major complications following core biopsy. CONCLUSIONS: Sonographically guided core biopsy provides an accurate and safe alternative to FNAC in the assessment of thyroid nodules.