Publications by authors named "Vedang Murthy"

109 Publications

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy.

Urol Oncol 2021 Feb 8. Epub 2021 Feb 8.

Department of Radiation Oncology, Tata Memorial Centre (TMH/ACTREC), Mumbai, India; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, India.

Purpose: We report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.

Materials And Methods: The study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.

Results: Of the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3-18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16-9.73, P = 0.02) and 5.27 (95% CI 1.87-14.84, P = 0.002) for IR and HR respectively, with LR as reference.

Conclusion: LRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.015DOI Listing
February 2021

Concurrent chemoradiotherapy for locally advanced unresectable adenoid cystic carcinoma of head and neck: experience from a single institute.

Eur Arch Otorhinolaryngol 2021 Feb 9. Epub 2021 Feb 9.

Department of Radiation Oncology, Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Dr. E. Borges Road, Parel, Mumbai, Maharashtra, 400012, India.

Purpose: To analyze the outcome of locally advanced unresectable adenoid cystic carcinoma (ACC) of head and neck treated with radical concurrent chemoradiotherapy (CRT) at a single tertiary care centre.

Methods: Between 2011 and 2018, 23 patients with locally advanced unresectable ACC of head and neck treated with non-surgical radical treatment with concurrent chemoradiotherapy were evaluated for outcome and toxicity. All but one patient received cisplatin-based concurrent chemotherapy and 74% of patients were treated with intensity-modulated radiotherapy.

Results: Median follow-up was 53 months (range 3-115 months). Following treatment, 11 patients achieved complete response (47.8%) and of the 12 patients with residual disease, 7 patients additionally had disease stabilization without local progression. Overall 15 patients had disease progression. Median time to progression was 28 months (range 6-67 months). The 3-year and 5-year overall survival, local progression-free survival (LPFS) and distant progression-free survival (DPFS) were 78%, 79.7%, 67.4% and 63%, 50.9%, 48.6%, respectively. Acute grade 3 mucositis was observed in three patients, and one patient additionally developed grade 4 neutropenia with subsequent complete recovery. No grade 3 or higher late toxicity was observed.

Conclusion: Radical concurrent chemoradiotherapy is a promising treatment option in locally advanced unresectable ACC with acceptable toxicity.
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http://dx.doi.org/10.1007/s00405-021-06654-3DOI Listing
February 2021

Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial.

J Clin Oncol 2021 Jan 26:JCO2003282. Epub 2021 Jan 26.

Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India.

Purpose: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.

Methods: This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).

Results: From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; < .0001). WPRT also showed higher 5-year DFS (89.5% 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; = .002), but 5-year OS did not appear to differ (92.5% 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; = .83). Distant metastasis-free survival was also higher with WPRT (95.9% 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups.

Conclusion: Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.
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http://dx.doi.org/10.1200/JCO.20.03282DOI Listing
January 2021

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients.

Int J Radiat Oncol Biol Phys 2021 Jan 23. Epub 2021 Jan 23.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries.

Methods And Materials: Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy.

Results: Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%.

Conclusions: These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.016DOI Listing
January 2021

Blood testis barrier revisited-Analysis of post-chemotherapy germ cell tumor orchidectomy and retroperitoneal lymph node dissection specimens.

J Surg Oncol 2021 Mar 11;123(4):1157-1163. Epub 2021 Jan 11.

Homi Bhabha National Institute, Mumbai, India.

Objective: To assess the response of chemotherapy on the primary tumor, compare it with the response in retroperitoneal disease, and study factors associated with pathological complete response.

Methods: We conducted a retrospective audit of all high inguinal orchidectomies (HIOs) performed after chemotherapy between 2012 and 2019 at a tertiary cancer center in India. Patient characteristics and histopathological response were extracted from electronic medical records, and predictors of testicular disease response were assessed.

Results: Of the 260 retroperitoneal lymph node dissections (RPLNDs) performed in the study period, 37 HIOs (14.23%) were carried out after chemotherapy. The median age of presentation was 28 years (16-41). Histopathology was divided into a viable tumor, mature teratoma, and necrosis/scarring. Residual disease was seen in 17 RPLND (46.0%) and 18 HIO (48.6%) specimens respectively. Of these 18, three patients had a residual viable tumor in the testis, and the remaining had a mature teratoma. Clinico-radiological assessment showed an average reduction of 61% in testicular disease size following chemotherapy. On orchidectomy histopathological assessment, the median tumor size was 9, 4, and 1.5 cm in specimens with a viable tumor, mature teratoma, and necrosis/scarring, respectively.

Conclusions: A low threshold for upfront chemotherapy in patients with a high disease burden may be considered as tumors within the testis respond to chemotherapy in more than half of the patients. Discordance rates of residual cancer in RPLND and HIO specimens exist but post-chemotherapy tumor size in testis correlates with the presence of a residual viable tumor.
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http://dx.doi.org/10.1002/jso.26374DOI Listing
March 2021

Implications of limited exolaryngeal disease and cricoarytenoid joint involvement in organ conservation protocols for laryngopharyngeal cancers: Results from a prospective study.

Head Neck 2020 Dec 26. Epub 2020 Dec 26.

Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.

Background: To identify clinicoradiological factors that determine functional outcomes in laryngopharyngeal cancers treated with chemoradiotherapy.

Methods: One hundred patients of locally advanced laryngopharyngeal cancers who were treated with chemoradiotherapy were accrued in this prospective study. The coprimary endpoint of the study was local control (LC) and functional larynx preservation survival (FLPS).

Results: The median follow-up was 39 months. Thirty-nine patients had a local failure of which 17 underwent a salvage laryngectomy. A dysfunctional larynx with clinic-radiologically disease was seen in only 1 patient. Factors significant for LC were thyroid cartilage erosion/lysis and cricoarytenoid joint involvement. Within the T4a subset, patients with exolaryngeal disease through the soft tissue framework had significantly better LC and FLPS than those with cartilage erosion/lysis.

Conclusions: Patients with limited exolaryngeal disease through the soft-tissue framework can be considered for functional organ preservation, while those with thyroid cartilage involvement and cricoarytenoid joint involvement are not suitable.
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http://dx.doi.org/10.1002/hed.26593DOI Listing
December 2020

Comprehensive Analysis of Low Molecular Weight Serum Proteome Enrichment for Mass Spectrometric Studies.

ACS Omega 2020 Nov 29;5(44):28877-28888. Epub 2020 Oct 29.

Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra 410210, India.

Rationale: The low molecular weight (LMW) proteins present in circulating body fluids, such as serum and plasma, hold biological significance as possible biomarkers. A major obstacle in mass spectrometry-based proteomics of serum is the presence of abundant high molecular weight proteins which mask the identification and quantitation of lower molecular weight proteins. Traditional methods involve the use of affinity resins to remove high molecular weight proteins, such as albumin and immunoglobulin G, with concomitant loss of lower molecular weight proteins. Considering the importance of depleting high molecular proteins, this paper compares an affinity resin, a gel-filter, and an acetonitrile (ACN) precipitation method to achieve successful removal of high molecular weight proteins and recovery of lower molecular weight proteins.

Methods: Serum enrichment was carried out by multiple methods such as with the commercially available serum protein mini kit, ACN precipitation, and a gel filter method. Mass spectrometric runs were carried out on an AB SCIEX ESI QTOF 5600 mass spectrometer. Mass spectrometry analysis of the enriched serum obtained by ACN precipitation and gel filter method was performed for global proteome profiling. Quantitative mass spectrometry using isobaric tags for relative and absolute quantitation (iTRAQ) for ACN-precipitated enriched serum was also carried out.

Results: The gel filter method, though allowing for the resolution and identification of LMW proteins, was better suited for global proteome analysis and not preferred for quantitative proteomic experiments. In contrast, enrichment by the ACN precipitation method allowed for the reproducible identification and quantitation of LMW proteins having molecular weight ≥4 kDa.

Conclusions: Using only chilled ACN and centrifugation, most of the highly abundant proteins were successfully removed from the serum, while recovering a significant portion of the LMW proteome. A more rapid protocol, which is compatible with iTRAQ labeling, to achieve improved results has been elucidated, thus allowing for better screening and identification of potential biomarkers.
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http://dx.doi.org/10.1021/acsomega.0c04568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659158PMC
November 2020

Pilot study comparing dominant intraprostatic lesion volume using Ga-68 prostate-specific membrane antigen PET-computed tomography and multiparametric MRI.

Nucl Med Commun 2020 Dec;41(12):1291-1298

Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Purpose: The standard imaging used for delineation of dominant intraprostatic lesion (DIL) is multiparametric MRI (mpMRI). The use of biologic imaging such as Ga-68 prostate-specific membrane antigen (PSMA) PET-computed tomography (PET-CT) for this purpose is being explored in view of increased sensitivity of this modality and the associated ease of delineation.

Materials And Methods: The primary objective of the study was to compare the autogenerated volumes of the DIL in Ga-68 PSMA PET-CT with the standard volume delineated in mpMRI. Twenty patients with biopsy-proven untreated prostatic adenocarcinoma were included. Multiple percentages of the maximum standardized uptake value (%SUVmax) were used to autogenerate DIL volumes in Ga-68 PSMA PET-CT and these volumes were numerically matched with the consensus DIL volume in mpMRI. PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were also calculated for each lesion.

Results: Median volume of DIL in mpMRI was 4 cm (interquartile range, IQR = 2.5-7.6 cm). The IQR for interobserver variability was 0.5-2.5 cm. Median SUVmax of the DIL was 14.1 (IQR = 10.2-22.3). Median %SUVmax corresponding to mpMRI volume was 41% of SUVmax (IQR = 34-55%). There was a strong negative correlation between MRI volume and %SUVmax (r = -0.829, P < 0.001). There was a significant correlation between TL-PSMA and prostate-specific antigen (r = 0.609, P = 0.004).

Conclusions: The median DIL volume was 4 cm and median %SUVmax corresponding to MR volume of DIL was 41%. A strong inverse relationship is found between mpMRI-defined DIL volume and the %SUVmax which generates similar volume in Ga-68 PSMA PET-CT. TL-PSMA could be a quantitative biomarker for tumor load and prognosis.
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http://dx.doi.org/10.1097/MNM.0000000000001283DOI Listing
December 2020

Mandatory preoperative COVID-19 testing for cancer patients-Is it justified?

J Surg Oncol 2020 Dec 25;122(7):1288-1292. Epub 2020 Aug 25.

Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Background: Severe acute respiratory syndrome coronavirus 2 has caused substantial disruptions in routine clinical care. Emerging data show that surgery in coronavirus disease (COVID)-positive cases can be associated with worsening of clinical outcomes and increased postoperative mortality. Hence, preoperative COVID-19 testing for all patients before elective surgery was implemented in our institution.

Materials And Methods: Two hundred and sixty-two asymptomatic cancer patients were preoperatively tested for COVID-19 using reverse-transcription polymerase chain reaction technique with nasopharyngeal and oropharyngeal swabbing. All negative patients were operated within 72 hours, and positive patients were quarantined for a minimum 14 days before re-swabbing.

Results: In our cohort, 21 of 262 (8.0%) asymptomatic preoperative patients, who were otherwise fit for surgery, tested positive. After adequate quarantine and a negative follow-up test report, 12 of 21 (57%) had an operation. No major postoperative morbidity due to COVID-19 was noted during the immediate postoperative period before discharge from the hospital.

Conclusion: Routine preoperative COVID-19 testing was successful in identifying asymptomatic viral carriers. There was no incidence of symptomatic COVID-19 disease in the postoperative period, and there was no incidence of morbidity attributable to COVID-19. These data suggested a beneficial role for mandatory preoperative COVID-19 testing.
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http://dx.doi.org/10.1002/jso.26187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461513PMC
December 2020

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane-based induction chemotherapy and concurrent chemo-radiotherapy in the modern era.

World J Otorhinolaryngol Head Neck Surg 2020 Mar 3;6(1):25-33. Epub 2020 Apr 3.

Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Objective: To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center.

Methods: We retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with "risk-adapted" intensity-modulated radiotherapy (IMRT) technique in all patients.

Results: After a median follow up of 45 months (range: 8-113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS ( = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications.

Conclusions: Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.
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http://dx.doi.org/10.1016/j.wjorl.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221210PMC
March 2020

Reply to Srinivas Chilukuri et al: The toxicity data from POP-RT: Proving the "Obvious" and challenging the "Norm".

Radiother Oncol 2020 Jun 7;147:248. Epub 2020 Apr 7.

Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India.

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http://dx.doi.org/10.1016/j.radonc.2020.03.041DOI Listing
June 2020

A Modified Histopathologic Staging in Penile Squamous Cell Carcinoma Predicts Nodal Metastasis and Outcome Better Than the Current AJCC Staging.

Am J Surg Pathol 2020 08;44(8):1112-1117

Departments of Pathology.

Recently, the American Joint Committee on Cancer (AJCC) updated the staging system for penile squamous cell carcinoma. According to it, unlike its previous version, the involvement of urethra does not upstage the tumor; however, the involvement of corpora cavernosa (CC) does. The tumors involving CC are now staged pT3, whereas those involving corpora spongiosa (CS) are staged pT2, irrespective of the involvement of the urethra. In the current study, we sought to validate these recent modifications and in-process also attempted to improvise upon it. The histopathology slides were reviewed in 142 cases of penile squamous cell carcinoma. The histopathologic variables noted were tumor grade, anatomic level of invasion (CC/CS), lymphovascular invasion (LVI), and perineural invasion (PNI). Metastases to the lymph nodes were confirmed. Tumors were staged pT2/pT3 according to AJCC 8th edition and this staging system was further improvised by incorporating histopathologic variables similar to pT1 tumors in AJCC 8th edition. Accordingly, pT2 tumors invaded CS/CC without LVI or PNI and were not grade 3, whereas pT3 tumors invaded CS/CC, showed LVI and/or PNI, or were grade 3. Both the staging models were then correlated with nodal metastasis and disease-free survival. The new staging model (P=0.001) and not the AJCC pT2/pT3 stages (P=0.2) showed a statistically significant correlation with nodal metastasis. Similarly, only the proposed model significantly impacted disease-free survival (P=0.011). To conclude, we were unable to validate the prognostic difference between the pT2/pT3 stages according to AJCC 8th edition. The staging system can be improvised by incorporating histopathologic variables similar to pT1 tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001490DOI Listing
August 2020

Study protocol of a randomised controlled trial of prostate radiotherapy in high-risk and node-positive disease comparing moderate and extreme hypofractionation (PRIME TRIAL).

BMJ Open 2020 02 28;10(2):e034623. Epub 2020 Feb 28.

Division of Uro-Oncology, Tata Memorial Centre, Mumbai, India.

Introduction: There has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.

Methods And Analysis: This is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.

Discussion: The trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.

Ethics And Dissemination: The trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.

Trial Registration Number: Registered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018.
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http://dx.doi.org/10.1136/bmjopen-2019-034623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050316PMC
February 2020

Tumor radiomic features complement clinico-radiological factors in predicting long-term local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancers.

Br J Radiol 2020 May 26;93(1109):20190857. Epub 2020 Feb 26.

Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK.

Objective: To study if pre-treatment CT texture features in locally advanced squamous cell carcinoma of laryngo-pharynx can predict long-term local control and laryngectomy free survival (LFS).

Methods: Image texture features of 60 patients treated with chemoradiation (CTRT) within an ethically approved study were studied on contrast-enhanced images using a texture analysis research software (TexRad, UK). A filtration-histogram technique was used where the filtration step extracted and enhanced features of different sizes and intensity variations corresponding to a particular spatial scale filter (SSF): SSF = 0 (without filtration), SSF = 2 mm (fine texture), SSF = 3-5 mm (medium texture) and SSF = 6 mm (coarse texture). Quantification by statistical and histogram technique comprised mean intensity, standard-deviation, entropy, mean positive pixels, skewness and kurtosis. The ability of texture analysis to predict LFS or local control was determined using Kaplan-Meier analysis and multivariate cox model.

Results: Median follow-up of patients was 24 months (95% CI:20-28). 39 (65%) patients were locally controlled at last follow-up. 10 (16%) had undergone salvage laryngectomy after CTRT. For both local control & LFS, threshold optimal cut-off values of texture features were analyzed. Medium filtered-texture feature that were associated with poorer laryngectomy free survival were entropy ≥4.54, ( = 0.006), kurtosis ≥4.18; = 0.019, skewness ≤-0.59, = 0.001, and standard deviation ≥43.18; = 0.009). Inferior local control was associated with medium filtered features entropy ≥4.54; p 0.01 and skewness ≤ - 0.12; = 0.02. Using fine filters, entropy ≥4.29 and kurtosis ≥-0.27 were also associated with inferior local control ( = 0.01 for both parameters). Multivariate analysis showed medium filter entropy as an independent predictor for LFS and local control ( < 0.001 & = 0.001).

Conclusion: Medium texture entropy is a predictor for inferior local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancer and this can complement clinico-radiological factors in predicting prognosticating these tumors.

Advances In Knowledge: Texture features play an important role as a surrogate imaging biomarker for predicting local control and laryngectomy free survival in locally advanced laryngo-pharyngeal tumors treated with definitive chemoradiation.
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http://dx.doi.org/10.1259/bjr.20190857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217564PMC
May 2020

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Eur Urol 2020 04 27;77(4):508-547. Epub 2020 Jan 27.

University of Bern, Bern, Switzerland; Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.

Objective: To present the results from the APCCC 2019.

Design, Setting, And Participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.

Outcome Measurements And Statistical Analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.

Results And Limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.

Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.

Patient Summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
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http://dx.doi.org/10.1016/j.eururo.2020.01.012DOI Listing
April 2020

Late toxicity and quality of life with prostate only or whole pelvic radiation therapy in high risk prostate cancer (POP-RT): A randomised trial.

Radiother Oncol 2020 Apr 7;145:71-80. Epub 2020 Jan 7.

Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India.

Aim: To report toxicity and quality of life (QOL) outcomes from a randomised trial of prostate only versus whole pelvic radiotherapy in high risk, node negative prostate cancer.

Materials/methods: Patients with localised prostate adenocarcinoma and nodal involvement risk > 20%, were randomised to prostate only (PORT, 68 Gy/25# to prostate) and whole pelvis (WPRT, 68 Gy/25# to prostate and 50 Gy/25# to pelvis) arms with stratification for TURP, Gleason score, baseline PSA, and type of androgen deprivation therapy (ADT). Image guided intensity modulated radiotherapy (IG-IMRT) and two years of ADT were mandatory. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using RTOG grading. QOL was assessed using EORTC QLQ-C30 and PR-25 questionnaire pre-treatment and every 3-6 months post RT.

Results: Total 224 patients were randomised (PORT 114, WPRT 110) from November 2011 to August 2017. Median follow up was 44.5 months. No RTOG grade IV toxicity was observed. Acute GI and GU toxicities were similar between both the arms. Cumulative ≥ grade II late GI toxicity was similar for WPRT and PORT (6.5% vs. 3.8%, p = 0.39) but GU toxicity was higher (17.7% vs. 7.5%, p = 0.03). Dosimetric analysis showed higher bladder volume receiving 30-40 Gy in the WPRT arm (V30, 60% vs. 36%, p < 0.001; V40, 41% vs. 25%, p < 0.001). There was no difference in QOL scores of any domain between both arms.

Conclusion: Pelvic irradiation using hypofractionated IG-IMRT resulted in increased grade II or higher late genitourinary toxicity as compared to prostate only RT, but the difference was not reflected in patient reported QOL. CLINICALTRIALS.GOV NCT02302105: Prostate Only or Whole Pelvic Radiation Therapy in High Risk Prostate Cancer (POP-RT).
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http://dx.doi.org/10.1016/j.radonc.2019.12.006DOI Listing
April 2020

Dose-escalation of radiation may improve outcomes of squamous cell carcinoma of bladder.

Clin Transl Radiat Oncol 2020 Jan 24;20:51. Epub 2019 Jul 24.

Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India.

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http://dx.doi.org/10.1016/j.ctro.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921205PMC
January 2020

68Ga-prostate-specific membrane antigen PETCT-based response to androgen deprivation therapy in patients with prostate cancer.

Nucl Med Commun 2019 Dec;40(12):1283-1288

Nuclear Medicine, Tata Memorial Centre and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute, Mumbai, India.

Objective: To assess the response of castration-naïve prostate cancer to androgen deprivation therapy (ADT) in Ga-PSMA PETCT, and test the hypothesis of differential response in primary, nodal and metastatic lesions.

Materials/methods: Patients with adenocarcinoma prostate with baseline Ga-prostate-specific membrane antigen (PSMA) PETCT scan, and response scan after 3-12 months of ADT from 2014 to 2017 were analyzed. Change in radiotracer uptake in the prostate, involved regional nodes and distant metastasis was semiquantitatively assessed in paired scans using maximum standardized uptake value (SUVmax). Response was categorized into complete or partial response (CR, PR) or stable disease or progressive disease (SD, PD), and correlated with known prognostic factors.

Results: Total 86 scans of 43 patients (17 metastatic, M+) were analyzed. After median 6 months of ADT, 0% primary, 23.3% nodes and 17.6% metastases showed CR; 18.6% primary, 8.3% nodes and 35% metastases showed PD. Prostate response was not significantly associated with any prognostic factor. Nodal response was higher in M0 than in M+ disease (CR 37 vs 4%, P = 0.003). Oligometastases responded better than polymetastases (CR/PR 62.5 vs 11.1%, P = 0.05). Decline in SUVmax of primary tumor correlated with decline in serum prostate-specific antigen (PSA) (90% of partial responders showed >80% decline in serum PSA vs 50% with PD, P = 0.06).

Conclusion: Primary prostatic tumor seems less likely to respond to ADT than nodal or metastatic lesions. Residual primary uptake may guide patient selection for local therapy in (oligo) metastatic prostate cancer.
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http://dx.doi.org/10.1097/MNM.0000000000001105DOI Listing
December 2019

Histopathological risk scoring system as a tool for predicting lymph nodal metastasis in penile squamous cell carcinoma.

Pathology 2019 Dec 18;51(7):696-704. Epub 2019 Oct 18.

Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Penile cancer is an aggressive neoplasm and nodal metastasis is a key factor in determining the outcome. While there is a paucity of tools predicting nodal metastasis, an elective groin node dissection (GND) may cause severe morbidity. We aimed to devise a histopathology-based risk stratification system to predict the risk of nodal metastasis in penile squamous cell carcinoma (SCC) patients. In this retrospective clinicopathological analysis, consecutive penile SCC patients who had undergone primary surgical treatment with GND from 2007 to 2012 were included. Histopathology slides were reviewed and a histopathological risk scoring system (ranging from 3 to 9) was devised by adding the values assigned to the following pathological variables: tumour grade (1-3); anatomical level of infiltration (1-3); and tumour infiltration pattern (1-3). Three risk groups were created based on histopathological risk scores. Final scores and risk groups were correlated with nodal metastasis, disease-free survival (DFS) and overall survival (OS). We also validated the earlier described prognostic index score (PIS) on our set of patients and compared it to our proposed scoring system. A total of 162 cases of primary penile resections with unilateral or bilateral groin node dissection were identified during the study period. Sixty-two of 68 patients (91.17%) and 58 of 94 patients (61.7%) had nodal metastasis on upfront and follow-up nodal basin surgeries, respectively. Chances of nodal metastasis for each risk group were as follows: low risk (score 3 and 4) 14.3%; intermediate risk (score 5) 52.6%; and high risk (scores 6-9) 83.7%. Follow-up was available in 145 patients (89.5%). Median follow-up was 21 months (1-96 months). The histopathological scoring system (p=0.04) and risk groups (p=0.005) had a statistically significant correlation with DFS but not with OS. Logistic regression model demonstrated that this stratification system was a good predictor of nodal metastasis. Further, this scoring system had better predictive sensitivity for detecting true node-negative cases and marginally better accuracy in detecting nodal metastasis as compared to the PIS. Our study demonstrates that the histopathological risk stratification can predict nodal metastasis and aid in planning management of penile cancer patients with judicious implementation of the morbid procedure of GND.
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http://dx.doi.org/10.1016/j.pathol.2019.08.003DOI Listing
December 2019

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Authors:
Elizabeth C Page Elizabeth K Bancroft Mark N Brook Melissa Assel Mona Hassan Al Battat Sarah Thomas Natalie Taylor Anthony Chamberlain Jennifer Pope Holly Ni Raghallaigh D Gareth Evans Jeanette Rothwell Lovise Maehle Eli Marie Grindedal Paul James Lyon Mascarenhas Joanne McKinley Lucy Side Tessy Thomas Christi van Asperen Hans Vasen Lambertus A Kiemeney Janneke Ringelberg Thomas Dyrsø Jensen Palle J S Osther Brian T Helfand Elena Genova Rogier A Oldenburg Cezary Cybulski Dominika Wokolorczyk Kai-Ren Ong Camilla Huber Jimmy Lam Louise Taylor Monica Salinas Lidia Feliubadaló Jan C Oosterwijk Wendy van Zelst-Stams Jackie Cook Derek J Rosario Susan Domchek Jacquelyn Powers Saundra Buys Karen O'Toole Margreet G E M Ausems Rita K Schmutzler Kerstin Rhiem Louise Izatt Vishakha Tripathi Manuel R Teixeira Marta Cardoso William D Foulkes Armen Aprikian Heleen van Randeraad Rosemarie Davidson Mark Longmuir Mariëlle W G Ruijs Apollonia T J M Helderman van den Enden Muriel Adank Rachel Williams Lesley Andrews Declan G Murphy Dorothy Halliday Lisa Walker Annelie Liljegren Stefan Carlsson Ashraf Azzabi Irene Jobson Catherine Morton Kylie Shackleton Katie Snape Helen Hanson Marion Harris Marc Tischkowitz Amy Taylor Judy Kirk Rachel Susman Rakefet Chen-Shtoyerman Allan Spigelman Nicholas Pachter Munaza Ahmed Teresa Ramon Y Cajal Janez Zgajnar Carole Brewer Neus Gadea Angela F Brady Theo van Os David Gallagher Oskar Johannsson Alan Donaldson Julian Barwell Nicola Nicolai Eitan Friedman Elias Obeid Lynn Greenhalgh Vedang Murthy Lucia Copakova Sibel Saya John McGrath Peter Cooke Karina Rønlund Kate Richardson Alex Henderson Soo H Teo Banu Arun Karin Kast Alexander Dias Neil K Aaronson Audrey Ardern-Jones Chris H Bangma Elena Castro David Dearnaley Diana M Eccles Karen Tricker Jorunn Eyfjord Alison Falconer Christopher Foster Henrik Gronberg Freddie C Hamdy Vigdis Stefansdottir Vincent Khoo Geoffrey J Lindeman Jan Lubinski Karol Axcrona Christos Mikropoulos Anita Mitra Clare Moynihan Gadi Rennert Mohnish Suri Penny Wilson Tim Dudderidge Judith Offman Zsofia Kote-Jarai Andrew Vickers Hans Lilja Rosalind A Eeles

Eur Urol 2019 12 16;76(6):831-842. Epub 2019 Sep 16.

Oncogenetics Team, Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK. Electronic address:

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.

Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.

Design, Setting, And Participants: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.

Outcome Measurements And Statistical Analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.

Results And Limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p =  0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p =  0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p =  0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).

Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.

Patient Summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.
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http://dx.doi.org/10.1016/j.eururo.2019.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880781PMC
December 2019

Initial experience of Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography imaging in evaluation of biochemical recurrence in prostate cancer patients.

World J Nucl Med 2019 Jul-Sep;18(3):244-250

Department of Nuclear Medicine and Molecular Imaging, Uro-Oncology Disease Management Group, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Gallium-68 labeled prostate-specific membrane antigen (Ga-68 PSMA) ligand (HBED-CC) is a novel tracer used for prostate cancer imaging. The aim of the study was to investigate the performance of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) after definitive treatment. Scans of 96 consecutive patients were analyzed. Sixty-two patients received external beam radiotherapy, 34 underwent radical prostatectomy (RP), and 20 patients were on androgen deprivation therapy. Patients with prostate-specific antigen (PSA) level ≥>0.2 ng/mL following RP and PSA rise by 2 ng/mL or more above the nadir PSA following RT (Phoenix criteria) was considered as BCR, respectively. All patients underwent contrast-enhanced PET/CT after injection of 67-111 MBq Ga-68 PSMA ligand. Detection rates were correlated with serum PSA level. Detection rate for nodal metastases was compared with CT. Results of the scan were validated by using either biopsy or follow-up imaging or clinical follow-up. Seventy-four (77%) patients showed abnormal finding in Ga-68 PSMA PET/CT. The median serum PSA level of the population was 5.5 ng/ml (range 0.2-123 ng/ml). The median PSA of the positive scans was higher than that of the negative scans (6 vs. 1.7 ng/ml) and was statistically significant ( = 0.001 by Mann-Whitney U-test). In post-RP group, the detection rates were 23%, 50%, and 82% for PSA <1, 1-2, and >2 ng/ml, respectively. For post-RT, the detection was 86%, 85%, and 95% for PSA 2-5, 5.1-10, and >10 ng/ml, respectively. PSMA PET/CT revealed nodal metastases in 52 (54%) patients while CT showed pathological nodes only in 27 (28%) patients. Overall PSMA PET/CT revealed more number of nodes than CT (111 vs. 48 nodal station). PSMA PET/CT showed relapse in prostate/prostatic bed in 26 (27%) patients, nodal metastases in 50 (52%), skeletal metastases in 20 (21%), and other sites in 4 (4%) patients. Ga-68 PSMA PET/CT has high detection rate for localizing the site of recurrence in patients with biochemical failure and is superior to CT scan in the detection of nodal disease.
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http://dx.doi.org/10.4103/wjnm.WJNM_47_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714163PMC
September 2019

Evaluation of quantitative imaging parameters in head and neck squamous cell carcinoma.

Q J Nucl Med Mol Imaging 2019 Sep 5. Epub 2019 Sep 5.

Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC), Tata Memorial Hospital (TMH), Tata Memorial Centre, Mumbai, India.

Background: Functional imaging such as 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), 18F-fluoro-misonidazole (F-MISO)-PET/CT, and diffusion-weighted magnetic resonance imaging (DW-MRI) can assess complex biological phenomena in tumors reflecting underlying disease biology. The aim of this prospective observational study was to correlate quantitative imaging parameters derived from pre-treatment biological imaging such as FDG-PET/CT, F-MISO-PET/CT, and DW-MRI with each other andì with clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive radio(chemo)therapy.

Methods: Twenty patients with pharyngo-laryngeal cancers underwent pre-treatment biological imaging. Gross tumor volume (GTV) was delineated on axial planning CT (GTVCT). Quantitative FDG-PET/CT parameters included maximum, mean, minimum standardized uptake values (SUVmax-FDG, SUVmean-FDG, SUVmin-FDG); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). F-MISO-PET/CT parameters included hypoxic tumor volume (HTV); maximum, mean, minimum SUV; and fractional hypoxic volume (FHV). Mean apparent diffusion coefficient (ADCmean) was derived from DW-MRI.

Results: There was moderately strong positive correlation (r=0.616, p=0.005) between GTVCT and MTV. HTV derived from F-MISO-PET/CT at 3-hours (HTV3hrs-F-MISO) showed strong positive correlation with GTVCT (r=0.753, p<0.0001) and MTV (r=0.796, p<0.0001) respectively. ADCmean showed strong positive correlations with SUVmean-5hrs-F-MISO (r=0.713, p=0.021) and SUVmin-5hrs-FMISO (r=0.731, p=0.016) respectively. A moderate negative correlation (r=-0.500, p=0.049) was observed between ADCmean and MTV. At a median follow up of 44 months, the 5-year Kaplan-Meier estimates of loco-regional control, disease-free survival, and overall survival were 53%, 43%, and 40% respectively. Larger volume of primary tumor (GTVCT>22cc and MTV>7.9cc) and increasing hypoxia (HTV3hr-F-MSO>4.9cc) were associated with worse outcomes.

Conclusions: Functional imaging represents an attractive and non-invasive modality to assess complex biological phenomena in solid tumors. Larger tumor volume and increasing hypoxia emerged as putative prognostic imaging biomarkers in HNSCC.
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http://dx.doi.org/10.23736/S1824-4785.19.03179-0DOI Listing
September 2019

Human SP-D Acts as an Innate Immune Surveillance Molecule Against Androgen-Responsive and Androgen-Resistant Prostate Cancer Cells.

Front Oncol 2019 11;9:565. Epub 2019 Jul 11.

Department of Innate Immunity, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.

Surfactant Protein D (SP-D), a pattern recognition innate immune molecule, has been implicated in the immune surveillance against cancer. A recent report showed an association of decreased SP-D expression in human prostate adenocarcinoma with an increased Gleason score and severity. In the present study, the SP-D expression was evaluated in primary prostate epithelial cells (PrEC) and prostate cancer cell lines. LNCaP, an androgen dependent prostate cancer cell line, exhibited significantly lower mRNA and protein levels of SP-D than PrEC and the androgen independent cell lines (PC3 and DU145). A recombinant fragment of human SP-D, rfhSP-D, showed a dose and time dependent binding to prostate cancer cells via its carbohydrate recognition domain. This study, for the first time, provides evidence of significant and specific cell death of tumor cells in rfhSP-D treated explants as well as primary tumor cells isolated from tissue biopsies of metatstatic prostate cancer patients. Viability of PrEC was not altered by rfhSP-D. Treated LNCaP (p53) and PC3 (p53 ) cells exhibited reduced cell viability in a dose and time dependent manner and were arrested in G2/M and G1/G0 phase of the cell cycle, respectively. rfhSP-D treated LNCaP cells showed a significant upregulation of p53 whereas a significant downregulation of pAkt was observed in both PC3 and LNCaP cell lines. The rfhSP-D-induced apoptosis signaling cascade involved upregulation of Bax:Bcl2 ratio, cytochrome c and cleaved products of caspase 7. The study concludes that rfhSP-D induces apoptosis in prostate tumor explants as well as in androgen dependent and independent prostate cancer cells via p53 and pAkt pathways.
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http://dx.doi.org/10.3389/fonc.2019.00565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637921PMC
July 2019

Prognostic value of response assessment fluorodeoxyglucose positron emission tomography-computed tomography scan in radically treated squamous cell carcinoma of head and neck: Long-term results of a prospective study.

J Cancer Res Ther 2019 Jul-Sep;15(3):596-603

Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Objective: The objective of this study is to evaluate the diagnostic and prognostic ability of fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy or radiotherapy only.

Materials And Methods: Fifty-nine patients with HNSCC planned for radical nonsurgical treatment were randomized to receive either three-dimensional conformal radiotherapy or intensity-modulated radiation therapy. In addition to routine clinical examination and staging investigations, patients had a FDG PET-CT scan at baseline and on the first follow-up for response assessment. No evidence of clinicopathological disease for at least 6 months after the completion of treatment was considered confirmation of complete response. The presence or absence of disease during the follow-up period was used to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET-CT for the primary site and node.

Results: At a median follow-up of 52.5 months, 55.6% of patients were alive and disease free. Response assessment PET-CT was done at a median of 9 weeks (range: 5-18 weeks). PET-CT assessment of the primary had sensitivity, specificity, PPV, and NPV of 81.8%, 93%, 75%, and 95.2%, respectively; the corresponding figures at the node were 44.4%, 95.6%, 66.7%, and 89.6%. The median baseline maximum standardized uptake value (SUV) at primary and node was 14.9 and 8.1, respectively. When PET-CT was done after 10 weeks, no false-positive or false-negative findings were seen. Patients with negative PET at the first follow-up had a significantly better progression-free and overall survival.

Conclusions: Disease evaluation using PET-CT has an overall accuracy of 80%. High baseline SUV correlates with worse clinical outcomes. Negative PET-CT at the first follow-up is a predictor for survival.
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http://dx.doi.org/10.4103/jcrt.JCRT_542_17DOI Listing
November 2019

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

Cancer 2019 09 31;125(18):3184-3197. Epub 2019 May 31.

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings.

Methods: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed.

Results: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01).

Conclusions: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.
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http://dx.doi.org/10.1002/cncr.32179DOI Listing
September 2019

Safety of Prostate Stereotactic Body Radiation Therapy after Transurethral Resection of Prostate (TURP): A Propensity Score Matched Pair Analysis.

Pract Radiat Oncol 2019 Sep - Oct;9(5):347-353. Epub 2019 Apr 9.

Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, India.

Purpose: To determine the genitourinary (GU) toxicity outcomes in prostate cancer patients treated with stereotactic body radiation therapy (SBRT) who have undergone a prior transurethral resection of prostate (TURP) and compare it to a similar non-TURP cohort.

Materials And Methods: Fifty prostate cancer patients who had undergone a single TURP, had a good baseline urinary function, and had been subsequently treated with SBRT were chosen from a prospectively maintained database. These were propensity score matched to a similar non-TURP cohort treated during the same period. Matching was done for diabetes mellitus and volume of radiation therapy. Acute GU and late GU toxicity were scored using the Radiation Therapy Oncology Group (RTOG) criteria. Stricture and incontinence were scored using Common Terminology for Common Adverse Events version 4.0.

Results: Median follow-up for the entire cohort was 26 months (non-TURP vs TURP, 30 months vs 22 months, P = .34). The median duration between TURP and start of SBRT was 10 months. There was no significant difference between non-TURP versus TURP cohort in terms of RTOG acute GU toxicities grade ≥2 (8% vs 6%, P = .45), RTOG late GU toxicities grade ≥2 (8% vs 12%, P = .10), stricture rates (4% vs 6%, P = .64), and incontinence rates (0% vs 4%, P = .15). The median duration of time to late toxicity was 16 months vs 10 months (P = .12) in non-TURP and TURP cohort, respectively.

Conclusions: Although modestly increased as compared with non-TURP patients, GU toxicities remains low with SBRT in post-TURP patients. SBRT can be safely performed in carefully selected post-TURP prostate cancer patients.
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http://dx.doi.org/10.1016/j.prro.2019.04.003DOI Listing
January 2020

Bladder cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India.

Indian J Cancer 2019 Jan-Mar;56(1):54-58

Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Background: Bladder cancer (BCa) is the ninth most common cancer accounting for 3.9% of all cancer cases as per the Indian Cancer Registry data. There is a scarcity of data on urinary Bca from India.

Aim: The aim of this study was to know demographic background, stage distribution, utilization of various treatment modalities, and oncological outcome in Indian patients presenting with bladder cancer to a tertiary care cancer center in Mumbai.

Methodology: We performed a retrospective audit of all patients registered as urinary BCa in our hospital from January 1, 2013 to December 31, 2013. Electronic medical records of these patients were checked for most of the information gathered.

Results: Median age of patients at presentation was 59 years with a range of 18-88 years. There were 84% male and 16% female patients. Forty seven percent of patients had nonmuscle invasive bladder cancer (NMIBC), 36% had muscle invasive bladder cancer and locally advanced disease, and 17% had metastatic disease. Eight patients were treated with trimodality bladder preservation protocol. Recurrence was seen in 38 (22.6%) patients with NMIBC. Out of them. 44.7% and 55.3% were in low- and high-grade tumors, respectively. Overall survival and disease-free survival estimated for 3 years were 63% and 57%, respectively.

Conclusion: Bladder cancer has a varied spectrum of presentation. Bladder cancer patients presenting to our hospital generally have a higher stage and grade of disease compared with that in the west.
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http://dx.doi.org/10.4103/ijc.IJC_351_18DOI Listing
August 2019

Effect of a planned training session on good clinical practice knowledge in research professionals: A pilot study.

Perspect Clin Res 2019 Jan-Mar;10(1):20-25

Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India.

Context: Adherence to good clinical practice (GCP) guidelines by the researcher provides public confidence that the rights, safety and well-being of human participants involved in research are protected. It has been observed that researchers require basic GCP training. Considering this, we had decided to conduct a training session on overview of GCP.

Aims: To strengthen the knowledge and awareness regarding GCP.

Settings And Design: The design of the study was quasi-experimental one group, pre-test and post-test design and the study was conducted at ACTREC among healthcare professionals at Tata Memorial Centre.

Methods And Material: A semi-structured questionnaire was used to collect the data in pre and post-test. A total of 138 participants were participated in the study. The training session was pre-planned which included a lecture followed by the question-answer session.

Statistical Analysis Used: Wilcoxon Signed Rank test was used to assess the effect of the planned teaching programme. Macnemar test was used for item wise comparison of pre and post-test scores. Mann Whitney test was used to determine the significant difference between knowledge scores and selected demographic variables.

Results: This study has resulted in overall improvement of knowledge with a median difference of 5 with -value <0.001. There was a statistically significant improvement of knowledge between pre and post-test of those having GCP training in the past, working group and education.

Conclusions: The exercise of holding training program was found to be significant in improving the knowledge base of participants, especially investigators and study coordinators.
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http://dx.doi.org/10.4103/picr.PICR_146_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371713PMC
March 2019

Positron Emission Tomography-Positive Post-Chemotherapy Seminoma Masses: Time to Reevaluate the Role of Radiotherapy?

J Clin Oncol 2019 04 27;37(11):937-938. Epub 2019 Feb 27.

Vedang Murthy, MD, and Carlton Johnny, MBBS, Tata Memorial Centre, Mumbai, India; and Robert Huddart, PhD, Institute of Cancer Research and Royal Marsden Hospital NHS, London, United Kingdom.

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http://dx.doi.org/10.1200/JCO.18.01991DOI Listing
April 2019