Publications by authors named "Ganesh Bakshi"

57 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2021.01.015DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.03282DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26374DOI Listing
March 2021

Extra-Uterine Low-Grade Endometrial Stromal Sarcoma Presenting as a Urinary Bladder Mass: a Case Report with Review of the Literature.

Indian J Surg Oncol 2020 Sep 15;11(Suppl 1):20-23. Epub 2019 Jul 15.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13193-019-00952-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534772PMC
September 2020

The Curious Case of Primary Prostatic Seminoma.

Urology 2020 Oct 3;144:e6-e9. Epub 2020 Aug 3.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2020.07.035DOI Listing
October 2020

Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature.

Indian J Cancer 2020 Jul-Sep;57(3):267-281

Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare low grade renal tumour exhibiting characteristic morphological features. We share our experience and discuss briefly, a review of the current literature.

Methods: Electronic medical records were searched between January 2005 to January 2017. The histopathology and immunohistochemistry slides were retrieved and reviewed.

Results: Eleven cases of MTSCC were identified. Mean age at presentation was 53.9 (age range 41 to 71) years with a slight female preponderance (F: M=6:5). Clinical stage at presentation was: Stage I (4 cases), Stage II (3 cases), Stage III (1 case), and Stage IV (3 cases). The average tumour size was 7.5cm (range 3.5 to 17cm). Microscopically, characteristic biphasic tumour with tubular and spindle cell morphology with variable mucinous stroma was noted in all. The prominent immunohistochemical profile revealed positivity for CK7 (7/8, 87.5%), AMACR (6/8, 75%), AE1/3 (4/4, 100%), CD10 (3/10, 27.3%), and Vimentin (3/3, 100%). Seven patients (Stage I and II) had been treated with nephrectomy, whereas only a diagnostic biopsy was available in four patients who presented with locally advanced disease (n=1) or distant metastasis (n=3) at presentation. The mean follow-up was 37.8 months (range 8 to 96 months), available in 10 out of 11 patients, without recurrence in nine while one died 8 months after diagnosis.

Conclusion: MTSCC is an indolent renal cancer with characteristic morphology. However, presentation with locally advanced disease or distant metastasis may be seen in a subset of these patients. This warrants close follow-up in even localized tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijc.IJC_642_18DOI Listing
December 2020

Thyroid-Like Follicular Carcinoma of the Kidney With Low-Grade Sarcomatoid Component: A Hitherto Undescribed Case.

Int J Surg Pathol 2020 Jul 10:1066896920940406. Epub 2020 Jul 10.

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

Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare subtype of renal cell carcinoma, which closely resembles follicular neoplasms of the thyroid and has a distinctive indolent clinical behavior. Until now, a single case of TLFCK with extensive sarcomatoid differentiation has been documented with aggressive clinical course. We present an unusual case of sarcomatoid TLFCK with a low-grade spindle cell component in a 34-year-old male patient, with an indolent course following radical nephrectomy and regional node dissection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1066896920940406DOI Listing
July 2020

Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

Ann Surg 2020 09;272(3):e249-e252

Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Ernest Borges Marg, Parel, Mumbai, India.

Background: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots.

Methods: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020.

Findings: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection.

Interpretation: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299113PMC
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001490DOI Listing
August 2020

Renal granulomas mimicking as malignant renal masses on F18 FDG PET/CT in a case of urothelial carcinoma.

Eur J Nucl Med Mol Imaging 2020 11 10;47(12):2930-2931. Epub 2020 Mar 10.

Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges Road, Parel, Mumbai, 400 012, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-020-04728-8DOI Listing
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-034623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050316PMC
February 2020

An invited commentary on "Assessing the impact of different distal ureter management techniques during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma on oncological outcomes: A systematic review and meta-analysis" [Int. J. Surg. 2020; Epub ahead of print].

Authors:
Ganesh K Bakshi

Int J Surg 2020 04 15;76:5-6. Epub 2020 Feb 15.

Department of Surgical Oncology [Uro oncology], Tata Memorial Hospital, Homi Bhabha National Institute, Parel, 400012, Mumbai, India. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijsu.2020.02.006DOI Listing
April 2020

Management of clinically node-negative groin in patients with penile cancer.

Indian J Urol 2020 Jan-Mar;36(1):8-15

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

Malignant penile neoplasms are commonly squamous etiology, with the inguinal nodes being the first echelon of spread. The disease spreads to the pelvic lymph nodes only after metastases to the groin nodes, and this is the most important prognostic factor in penile carcinoma. While treatment of penile carcinoma with proven metastases to the inguinal lymph nodes mandates ilioinguinal lymph node dissection, the treatment of patients with impalpable nodes is more controversial. Overtreatment leads to excessive treatment-related morbidity in these patients, while a wait-and-see policy runs the risk of patients presenting with inguinal and distant metastases, which would have been curable at presentation. Unfortunately, no single imaging modality has been proved to be convincingly superior in the staging, and hence, management of the clinically negative groin has been subject to debate. While some high volume centers have promoted the use of dynamic sentinel lymph node biopsy, others advocate the use of the modified inguinal lymph node template to stage the groin adequately. Newer techniques such as video endoscopic inguinal lymph node dissection have been introduced as an alternative to the original radical inguinal lymphadenectomy to reduce morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/iju.IJU_221_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961429PMC
January 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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2019.12.006DOI Listing
April 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pathol.2019.08.003DOI Listing
December 2019

Therapeutic efficacy, prognostic variables and clinical outcome of Lu-PSMA-617 PRLT in progressive mCRPC following multiple lines of treatment: prognostic implications of high FDG uptake on dual tracer PET-CT vis-à-vis Gleason score in such cohort.

Br J Radiol 2019 Dec 1;92(1104):20190380. Epub 2019 Nov 1.

Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, JerbaiWadia Road, Parel, Mumbai, India.

Objective: To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of Lu-PSMA-617 PSMA targeted radioligand therapy (PRLT) in the setting of heavily pre-treated metastatic castrate-resistant prostate cancer (mCPRC) patients and also examine the association of prognostic variables with therapeutic outcome in such patient cohort.

Methods: We examined the medical records of mCRPC patients who had undergone Lu-PSMA-617 PRLT from March 2017 to February 2019 in our institute. Patients receiving equal to or more than two cycles were included and analyzed in this retroprospective study.The Ga-PSMA-11 PET-CT and 18-fludeoxyglucose positron emission tomography (FDG PET)-CT scan findings, serum prostate-specific antigen (PSA) change, health-related quality of life (HRQoL) scales (Eastern Cooperative Oncology Group/Karnofsky score) and Gleason score were assessed for their implications on the outcome of therapy. The treatment response was evaluated under three categories: (a) symptomatic (b) biochemical and (c) imaging response.The PFS and OS following first PRLT were determined and the association of various variables with PSA doubling time (DT) and FDG uptake in the lesions were analyzed. Toxicity assessment was undertaken objectively by National Cancer Institute-Common Terminology Criteria for Adverse Events scale v. 5.0 for haematological and nephrotoxicity, and salivary gland toxicity assessed by xerostomia inventory score.

Results: A total of 40 mCRPC patients (age range: 46-84 years; median 63 years), who had undergone Lu-PSMA-617 PRLT, of at least two cycles was identified and selected for the analysis. FDG uptake was noted in 87.5% of patients ( = 35). Out of 40 cases, 21 were responders (CR, PR and SD) and 19 were non-responders (PD) on symptomatic and biochemical scales while on molecular imaging response, 16 (43%) were responders and remaining 21 (57%) were non-responders. Lesion-wise, Ga-PSMA-11 avid metastatic nodal disease responded well with Lu PSMA-617 PRLT, as compared to hepatic and skeletal lesions. The median OS and PFS was 12 and 7 months respectively following first PRLT. Patients with negative serum PSA-DT demonstrated superior 1 year PFS as compared to those with positive serum PSA-DT (52.5 47.5%) ( = 0.029). Patients receiving greater than two cycles PRLT demonstrated a higher negative PSA-DT as compared to those receiving two cycles (-value = 0.03). Grade 1 xerostomia was observed in two patients (5%) (mean xerostomia score of 23), haematotoxicity in seven patients [Grade I ( = 2, 5%) and Grade II ( = 5, 14%)].

Conclusion: Lu-PSMA-617 PRLT was well-tolerated and able to produce disease control with good symptomatic and biochemical responses in the context of heavily pre-treated mCRPC with progressive disease, with low toxicity profile. Evident association of high FDG uptake was observed with aggressive disease biology coupled with increasing Gleason score and poorer 12 months PFS. Negative PSA-DT following therapy demonstrated longer PFS. The results demonstrate important future role of Lu-PSMA-617 PRLT in the treatment of mCRPC.

Advances In Knowledge: The present work explored in a large teriary cancer care setting, the efficacy of Lu-PSMA-617 PRLT, in an aggressive and unselected subset of mCRPC. The response and outcome was correlated with a number of prognostic variables, including molecular imaging findings (FDG uptake in the metastatic lesions), PSA DT and Gleason score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20190380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913363PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/wjnm.WJNM_47_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714163PMC
September 2019

Incidental Detection of Pleomorphic Sarcoma on 68Ga-PSMA PET/CT in a Patient With Prostate Cancer.

Clin Nucl Med 2020 Feb;45(2):e120-e121

From the Departments of Nuclear Medicine and Molecular Imaging.

Ga prostate-specific membrane antigen (PSMA) PET/CT is used in the staging, evaluation of biochemical recurrence, and response assessment of patients with prostate cancer. In addition to the PSMA-expressing prostate cancer cells, Ga-PSMA binds to the neovasculaature of various other solid tumors and benign lesions. We report a case of a 72-year-old man with recently diagnosed adenocarcinoma of prostate, incidentally found to have pleomorphic sarcoma on the staging Ga-PSMA PET/CT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000002760DOI Listing
February 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637921PMC
July 2019

Radiological differentiation of phaeochromocytoma from other malignant adrenal masses: importance of wash-in characteristics on multiphase CECT.

Endocr Connect 2019 07;8(7):898-905

Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India.

Rationale And Introduction: To evaluate the computerised tomography (CT) characteristics of phaeochromocytoma (PCC) that differentiate them from other non-benign adrenal masses such as adrenocortical carcinoma (ACC), primary adrenal lymphoma (PAL) and adrenal metastases (AM).

Methods: This retrospective study was conducted at a tertiary health care institute from Western India. Patients presented between January 2013 and August 2016 with histological diagnosis of PCC or other non-benign adrenal mass having adequate reviewable imaging data comprising all four CECT phases were included.

Results: The study cohort consisted of 72 adrenal masses from 66 patients (33 PCC, 22 ACC, 4 PAL, 13 AM). Unlike other masses, majority of PCC (25/33) showed peak enhancement in early arterial phase (EAP). PCC had significantly higher attenuation in EAP and early venous phase (EVP), and higher calculated percentage arterial enhancement (PAE) and percentage venous enhancement (PVE) than other adrenal masses (P < 0.001). For diagnosis of PCC with 100% specificity, PAE value ≥100% and EAP attenuation ≥100 HU had 78.8 and 63.6% sensitivity respectively. ACC were significantly larger in size as compared to PCC and metastasis. The adreniform shape was exclusively found in PAL (two out of four) and AM (4 out of 13). None of the enhancement, wash-in or washout characteristics were discriminatory among ACC, PAL and AM.

Conclusion: Peak enhancement in EAP, PAE value ≥100% and EAP attenuation ≥100 HU differentiate PCC from other malignant adrenal masses with high specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-19-0198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599213PMC
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijc.IJC_351_18DOI Listing
August 2019

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

Indian J Cancer 2017 Oct-Dec;54(4):601-604

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

Introduction: The stage at diagnosis of renal cell cancer (RCC) in developed countries is lower due to increased utilization of routine health checkups by patients compared to developed countries. This study aims to determine the sociodemographic and clinical distribution of RCC in patients presenting to Tata Memorial Hospital (TMH).

Subjects And Methods: We performed a retrospective audit of all patients presenting to TMH with a diagnosis of RCC. Data were retrieved from our electronic medical record system from January 1, 2013 to December 31, 2013. The survival analysis was done by Kaplan-Meir analysis method of estimating survival. Log-rank test of comparison was applied to estimate the difference in the survival among the different stages of renal cancer.

Results: Of the 35,197 new registered patients at TMH, 338 were diagnosed with RCC. Most patients were in the 50-60 years age group, with 56.6 years being the median age at presentation. Among patients treated at TMH, 84 underwent surgery and tyrosine kinase inhibitor was given in 55 (16%) patients. The patients' characteristics, clinical characteristics of RCC, treatment modalities offered, and survival of patients treated for RCC are presented in this paper.

Conclusion: In the absence of robust Indian data on RCC, this audit provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at our center compared with the West.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijc.IJC_644_17DOI Listing
October 2018

Change in the ranking and increasing trend of the prostate cancer from the population-based cancer registries in India.

Indian J Urol 2018 Jul-Sep;34(3):235-236

Tata Memorial Centre, Mumbai, Maharashtra, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/iju.IJU_112_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034414PMC
July 2018

Genetic status determines F-FDG uptake in pheochromocytoma/paraganglioma.

J Med Imaging Radiat Oncol 2017 Dec 5;61(6):745-752. Epub 2017 Jun 5.

Department of Endocrinology, Seth G S Medical College and KEM Hospital, Mumbai, India.

Introduction: Although few studies have demonstrated utility of F- fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomography ( F-FDG PET/CT) in benign pheochromocytoma/paragangliomas (PCC/PGLs), there limited data on factors predicting the FDG uptake in PCC/PGL.

Methods: The study was conducted at a tertiary health care centre. In addition to the routine investigations, all patients (n = 96) with PCC/PGL were evaluated with F-FDGPET/CT and majority (n = 78) underwent I-metaiodobenzyl guanidine ( I-MIBG) scintigraphy. Forty-three patients also underwent testing for germline mutations in five PCC/PGL susceptibility genes (VHL, RET, SDHB, SDHC and SDHD) and all patients were evaluated clinically for neurofibromatosis-1.

Results: The study included 96 patients with PCC/PGL(82 benign and 14 malignant). FDGSUVmax was significantly higher for malignant than benign PCC/PGL(P = 0.009) and for extra-adrenal PGL than adrenal PCC (P = 0.017). In subgroup analysis, metanephrine-secreting PCC and non-secretory PCC had significantly lower FDG SUVmax than normetanephrine-secreting PCC (P = 0.017, P = 0.038 respectively), normetanephrine-secreting-sympathetic PGL (P = 0.008, P = 0.019 respectively) and non-secretory sympathetic PGL (P = 0.003, P = 0.009 respectively). Patients with mutations in cluster 1 genes (n = 14) had significantly higher FDG SUVmax than those with mutations in cluster 2 genes (n = 4) (P = 0.04). Sensitivities of I-MIBG and F-FDG PET/CTwere 77.78% and 100% for cluster 1 genes-related PCC/PGL whereas they were 100% and 50% for cluster 2 genes-related PCC/PGL, respectively. Multivariate regression analysis of mutation positive patients identified genetic status as the only independent predictor of FDG SUVmax.

Conclusion: The study suggests that the underlying genetic status determines FDG uptake in PCC/PGL and not location, secretory status or malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1754-9485.12620DOI Listing
December 2017

Development of Booklet on Male Sexual Dysfunction, its Measures and Assessing its Impact on Knowledge of Patients with Urological Cancers.

Asia Pac J Oncol Nurs 2016 Oct-Dec;3(4):382-389

Nursing Department, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Objective: Urological cancer and its surgeries have great impact on male sexuality which could have physical or emotional consequences. In India, speaking openly about the sexual matter is a taboo and an aspect considered forbidden. Therefore, the aim of the present study is to develop an information booklet about male sexual dysfunction and assess its impact on knowledge of patients with urological cancers.

Methods: Information booklet was developed after literature review, and its content validity was established. Reliability of the questionnaire was 0.95. A randomized control trail using pre- and post-test design was used for 30 male urological cancer patients and was assigned to experimental group (15) who received information booklet and control group (15) who received standard treatment. Subjects in the experimental group were provided with opinionnaire during posttest. Data were analyzed using descriptive and inferential statistics.

Results: In experimental group, 40% of the subjects were ≤ 40 years, whereas 27% in the control group ( = 0.699). The pre- and post-mean difference score was significantly higher in experimental group (mean difference - 5) than control group (mean difference - 0.4). All subjects (100%) opined that the information booklet was useful, adequate, self-explanatory, sequential, and clear.

Conclusions: Information in the booklet will help subjects to understand the common sexual problems after urological surgeries and help them to cope with the problems, thereby improving their quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2347-5625.196495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214872PMC
January 2017

Predictors of malignancy in patients with pheochromocytomas/paragangliomas: Asian Indian experience.

Endocr Connect 2016 Nov 16;5(6):89-97. Epub 2016 Nov 16.

Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, India.

Background And Aims: Malignant transformation of pheochromocytomas/paragangliomas (PCC/PGL) is a rare occurrence, and predictive factors for the same are not well understood. This study aims to identify the predictors of malignancy in patients with PCC/PGL.

Materials And Methods: We performed a retrospective analysis of 142 patients with either PCC or PGL registered at our institute between 2000 and 2015. Records were evaluated for clinical parameters like age, gender, familial/syndromic presentation, symptomatic presentation, biochemistry, size, number and location of tumours and presence of metastases and mode of its diagnosis.

Results: Twenty patients were found to have metastases; 13 had metastases at diagnosis and seven during follow-up. Metastases were detected by radiology (CT-neck to pelvis) in 11/20 patients (5/13 synchronous and 6/7 metachronous), I-metaiodobenzylguanidine in five (2/12 synchronous and 3/6 metachronous) patients and F-flurodeoxyglucose PET/CT in 15 (12/12 synchronous and 3/3 metachronous) patients. Malignant tumours were significantly larger than benign tumours (8.3 ± 4.1 cm, range: 3-22 cm vs 5.7 ± 2.3 cm, range: 2-14 cm, P = 0.0001) and less frequently metanephrine secreting. On linear regression analysis, tumour size and lack of metanephrine secretion were the independent predictors of malignancy.

Conclusions: Patients with primary tumour size >5.7 cm and lack of metanephrine secretory status should be evaluated for possible malignancy not only at diagnosis but also in the postoperative period. As compared to CT and I-MIBG scan, F-flurodeoxyglucose PET/CT analyses are better (sensitivity: 100%) for the diagnosis of metastases in our study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-16-0086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314950PMC
November 2016

Genitourinary cancers: Summary of Indian data.

South Asian J Cancer 2016 Jul-Sep;5(3):122-4

Department of Uro-oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Tumors of the genitourinary system are one of the most common tumors encountered in clinical practice. The associated morbidity and mortality and the significant proportion of affected middle-age individuals have a major bearing on the death-adjusted life years compared to other malignancies. Genitourinary system tumors encompass a very broad spectrum with regard to age, location, histology, and clinical outcomes. Advances in diagnostic imaging, surgical techniques, radiotherapy equipment, and generation of newer chemotherapeutic and targeted agents over the past few years have helped improving treatment outcome. Several focused groups within India have been working on a range of topics related to genitourinary system tumors, and a significant body of work from India in the recent years is being increasingly recognized throughout the world. The present article summarizes the key published work related to the epidemiology of genitourinary system tumors in the Indian setting. A PubMed search was made for locating and selecting articles relevant to the topic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2278-330X.187577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991131PMC
September 2016