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BACKGROUND: The evolution and outcomes of extended pancreatectomies at a single institute over 15 years are presented in this study. METHODS: A retrospective analysis of the institutional database was performed from 2015 to 2022 (period B). Patients undergoing extended pancreatic resections, as defined by the International Study Group for Pancreatic Surgery, were included. Perioperative and survival outcomes were compared with data from 2007-2015 (period A). Regression analyses were used to identify factors affecting postoperative and long-term survival outcomes. RESULTS: A total of 197 (16.1%) patients underwent an extended resection in period B compared to 63 (9.2%) in period A. Higher proportions of borderline resectable (5 (18.5%) versus 51 (47.7%), P = 0.011) and locally advanced tumours (1 (3.7%) versus 24 (22.4%), P < 0.001) were resected in period B with more frequent use of neoadjuvant therapy (6 (22.2%) versus 79 (73.8%), P < 0.001). Perioperative mortality (4 (6.0%) versus 12 (6.1%), P = 0.81) and morbidity (23 (36.5%) versus 83 (42.1%), P = 0.57) rates were comparable. The overall survival for patients with pancreatic adenocarcinoma was similar in both periods (17.5 (95% c.i. 6.77 to 28.22) versus 18.3 (95% c.i. 7.91 to 28.68) months, P = 0.958). Resectable, node-positive tumours had a longer disease-free survival (DFS) in period B (5.81 (95% c.i. 1.73 to 9.89) versus 14.03 (95% c.i. 5.7 to 22.35) months, P = 0.018). CONCLUSION: Increasingly complex pancreatic resections were performed with consistent perioperative outcomes and improved DFS compared to the earlier period. A graduated approach to escalating surgical complexity, multimodality treatment, and judicious patient selection enables the resection of advanced pancreatic tumours.
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Pancreatectomy , Pancreatic Neoplasms , Humans , Male , Female , Retrospective Studies , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Middle Aged , Aged , Treatment Outcome , Combined Modality Therapy , Neoadjuvant Therapy , Postoperative Complications/epidemiology , AdultABSTRACT
BACKGROUND: 'Textbook Outcome' (TO) represents an effort to define a standardized, composite quality benchmark based on intraoperative and postoperative endpoints. This study aimed to assess the applicability of TO as an outcome measure following liver resection for hepatic neoplasms from a low- to middle-income economy and determine its impact on long-term survival. Based on identified perioperative predictors, we developed and validated a nomogram-based scoring and risk stratification system. METHODS: We retrospectively analyzed patients undergoing curative resections for hepatic neoplasms between 2012 and 2023. Rates of TO were assessed over time and factors associated with achieving a TO were evaluated. Using stepwise regression, a prediction nomogram for achieving TO was established based on perioperative risk factors. RESULTS: Of the 1018 consecutive patients who underwent liver resections, a TO was achieved in 64.9% (661/1018). The factor most responsible for not achieving TO was significant post-hepatectomy liver failure (22%). Realization of TO was independently associated with improved overall and disease-free survival. On logistic regression, American Society of Anesthesiologists score of 2 (p = 0.0002), perihilar cholangiocarcinoma (p = 0.011), major hepatectomy (p = 0.0006), blood loss >1500 mL (p = 0.007), and presence of lymphovascular emboli on pathology (p = 0.026) were associated with the non-realization of TO. These independent risk factors were integrated into a nomogram prediction model with the predictive efficiency for TO (area under the curve 75.21%, 95% confidence interval 70.69-79.72%). CONCLUSION: TO is a realizable outcome measure and should be adopted. We recommend the use of the nomogram proposed as a convenient tool for patient selection and prognosticating outcomes following hepatectomy.
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Backgrounds/Aims: A postoperative biliary leak is one of the most morbid complications occurring after a liver resection, the long-term impact of which remains unknown. Methods: Retrospective analysis of consecutive liver resections performed from 1 January 2011 to 31 December 2021. Primary endpoint of disease-free survival (DFS) was compared between patients with and without a bile leak, stratifying for tumor type. Survival curves were plotted using Kaplan-Meier estimates, and differences between them were analyzed using the log-rank test. Results: In toto, 862 patients were analyzed, and included 306 (35.5%) hepatocellular carcinomas, 212 (24.6%) metastatic colorectal cancers, and 111 (12.9%) cholangiocarcinomas (69 intrahepatic cholangiocarcinomas, 42 hilar cholangiocarcinomas). Occurrence of a bile leak was associated with significantly poorer DFS only in patients with cholangiocarcinoma (median DFS 9.9 months vs. 24.9 months, p = 0.013), and further analysis was restricted to this cohort. A Cox regression performed for factors associated with DFS detriment in patients with cholangiocarcinoma showed that apart from node positivity (hazard ratio [HR]: 2.482, p = 0.033) and margin positivity (HR: 2.65, p = 0.021), development of a bile leak was independently associated with worsening DFS on both univariate and multiple regression analyses (HR: 1.896, p = 0.033). Conclusions: Post-hepatectomy biliary leaks are associated with significantly poorer DFS only in patients with cholangiocarcinoma, but not in patients with hepatocellular carcinoma or metastatic colorectal cancer. Methods to mitigate this survival detriment need to be explored.
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BACKGROUND: Outside of clinical trials, real-world data of advanced gastric cancers (AGCs) managed with perioperative or adjuvant chemotherapy with a backbone of D2 lymphadenectomy is limited. PATIENTS AND METHODS: Curative resections for gastric adenocarcinoma between January 2003 and January 2020 at the Tata Memorial Centre were analyzed, comparing three time periods marking major increments in annual gastric resections (GRs). RESULTS: 1657 radical gastric resections were performed with a morbidity and mortality rate of 34.9% and 1.4%, respectively. Over three consecutive periods, the number of annual GRs increased from 56/year to 97/year to 156/year (P < 0.001) with a significant escalation in surgical magnitude and complexity. Improvement in surgical quality indicators (median lymph node yield from 15 to 25, P < 0.001 and margin negativity from 8.2 to 5.5%, P = 0.002) was observed with no corresponding increase in severe complications (6.9%) or mortality (1.4%). The proportion of distal and signet ring cancers was found to decrease over time, with an increase in proximal cancers and younger age at presentation. Overall, 90% of GRs were for AGCs with a median overall survival (OS) of 4.4 years (± 6 months), and 5-year OS rate of 47.6% (± 1.9%). CONCLUSIONS: Change in pattern of tumor characteristics was observed. Aggressive treatment options for AGC were employed progressively with excellent survival. With increase in volumes, improvements in surgical quality indicators, and a relative improvement in postoperative mortality was observed. These results provide a roadmap for developing dedicated gastric cancer centers.
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Introduction: Circulating tumor cells are a promising biomarker in many malignancies. CTC dissemination during the operative procedure can lead to disease recurrence. The effect of preoperative transarterial embolization on the release of CTCs and miRNA panels and oncological outcomes in large hepatocellular carcinomas has been evaluated. Materials and methods: The study included non-metastatic HCC >5 cm in size, that were completely resected after TAE (n = 10). Blood was collected pre-TAE, post-TAE, postoperative (day 2,30 and 180) and analyzed for the presence of CTC and miRNA (miR-885-5p, miR-22-3p, miR-642b-5p). The samples were subjected to CTC enrichment, isolation and staining using the markers CD45, EpCAM, and cytokeratin (CK). The data was analyzed using Gene Expression Suite software. Results: The CTC enumeration resulted in three groups: Group 1- CTC present at both pre-TAE and postoperative day 30 (n = 4), Group 2- CTC present at pre-TAE and clearing at postoperative day 30 (n = 2), Group 3- No CTC detected at any stages (n = 3). Group 2 patients had better survival compared with the other groups. Downregulation of miRNA 22-3p also had favorable prognostic implications. Conclusion: Although preoperative TAE does not seem to impact CTC shedding, CTC clearance may prove to be a valuable biomarker in prognosticating HCC. A larger study to evaluate the significance of CTCs as a prognostic marker is warranted to further evaluate these findings.
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Purpose: We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Materials and Methods: Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Results: Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. Conclusions: IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.
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BACKGROUND: Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases. OBJECTIVE: To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years. METHODS: Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed. RESULTS: The mean age of the sample was 11.4 months (95% CI, 10.9-11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2-89.2%), which increased to 92.1% (95% CI, 84.3-96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4-99.9%). CONCLUSION: CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.
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Data on radiofrequency ablation (RFA) in tumor-induced osteomalacia (TIO) are restricted to case reports (~ 11 patients) and long-term follow-up data are further scarce. We describe our experience on managing TIO from a tertiary care center in India. Retrospective study of patients with localized TIO was performed and clinical, biochemical, treatment and follow-up details were retrieved. Normalization of serum phosphorus in absence of phosphate supplementation was defined as remission. Of 33 patients (23 males), 24 patients underwent surgery as first-line treatment, and early remission, delayed remission (> 1 month for phosphorus normalization) and persistence were observed 12, 3, and 9 patients at a median follow-up of 5 (4-9) years. The gender, age, tumor size, location of tumors and FGF23 levels were not statistically different in patients who were in remission after surgery versus those with persistent disease. Second/third line treatment included conventional medical treatment and/or repeat surgery (n = 3), radiotherapy (n = 3), peptide receptor radionuclide therapy (n = 1), RFA (n = 1). Two patients had transient worsening (weeks) of weakness post-surgery. 10 patients underwent RFA (first-line n = 9); at the last follow-up 5 (4-10) years, 7 are in remission. Two of three persistent disease patients had large tumors (5.6 and 3.6 cm). There were no RFA-related complications except local ulcer in one. Although persistent disease was present in a few patients in both arms, there was no recurrence in either RFA or surgical cohort. RFA provide durable response similar to surgery, persistence requires multi-modality treatment.
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PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.
Subject(s)
Administration, Metronomic , Fibromatosis, Aggressive , Methotrexate , Tertiary Care Centers , Humans , Male , Female , Adult , Fibromatosis, Aggressive/drug therapy , Fibromatosis, Aggressive/mortality , Fibromatosis, Aggressive/economics , India , Tertiary Care Centers/statistics & numerical data , Young Adult , Middle Aged , Adolescent , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methotrexate/economics , Standard of Care , Child , Vinblastine/administration & dosage , Vinblastine/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Tamoxifen/administration & dosage , Tamoxifen/economics , Tamoxifen/therapeutic use , Retrospective StudiesABSTRACT
Hepatic artery infusion chemotherapy (HAIC) is a popular treatment modality for the treatment of colorectal liver metastasis (CRLM). The aim of this study was to determine the feasibility of HAIC for high-risk resected CRLM delivered using repeated femoral puncture and delivering 5-fluorouracil infusional chemotherapy along with systemic adjuvant chemotherapy. The present study is a retrospective review of a prospectively maintained database. All patients who underwent HAIC for colorectal liver metastases between July 2022 and July 2023 were included. A total of 12 patients were included in the study of which 11 completed four sessions as planned. The median age was 47 (29-73) years with nine male (81%) and two female (18%) patients. Rectum (n = 7, 63%) was the most common primary location. All patients received systemic chemotherapy with 5-fluorouracil-based regimens prior to HAIC (median 12 cycles). The median number of metastasis was 2 (1-8). Eight patients had metastasis in unilobar distribution (73%). On completion of HAIC treatment, nine patients (64%) were completely disease free with a median follow-up of 8 months. None of the patients experienced any immediate adverse events during or after completion of the procedure. Conventional HAIC comes with various challenges such as unavailability of the agent floxuridine and the specialized HAIC pump. Percutaneous HAIC has a lower chance of infection. The delivery of HAIC using repeated femoral punctures and 5FU chemotherapy was successful in over 90% of the patients making it a feasible option in the treatment of CRLM.
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PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.
Subject(s)
Meningeal Neoplasms , Meningioma , Octreotide , Octreotide/analogs & derivatives , Humans , Meningioma/radiotherapy , Meningioma/diagnostic imaging , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/diagnostic imaging , Female , Male , Octreotide/therapeutic use , Octreotide/administration & dosage , Middle Aged , Adult , Organometallic Compounds/therapeutic use , Aged , Treatment Outcome , Radiopharmaceuticals/therapeutic use , Receptors, Peptide , Tertiary Care Centers , Disease ProgressionABSTRACT
Retinoblastoma (RB) is the most common childhood intraocular malignancy. Delayed presentation due to a lack of awareness and advanced intraocular tumors are a common scenario in low-middle income countries (LMICs). Remarkable treatment advances have been made in the past few decades allowing globe salvage in advanced intraocular RB (IORB) including systemic chemotherapy with focal consolidation and targeted treatments like intraarterial chemotherapy and intravitreal chemotherapy. However, a lack of availability and affordability limits the use of such advances in LMICs. External beam radiotherapy, despite risk of second cancers in RB with germline mutations, still remains useful for recalcitrant RB not responding to any other treatment. When choosing conservative treatment for advanced IORB, the cost and long duration of treatment, morbidity from multiple evaluation under anesthesias (EUAs), side effects of treatment and risk of treatment failure need to be taken into account and discussed with the parents. In this article, the authors discuss the ICMR consensus guidelines on the management of IORB.
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Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced stage presentation of RB is common in low middle-income countries (LMICs) due to lack of awareness, social taboos associated with enucleation, seeking alternative conservative treatment options, and poor accessibility to health care. Over the last few decades, there have been significant advancements in the management of extraocular RB (EORB) which have improved outcomes and helped in minimizing treatment-related toxicities. The incorporation of multimodality approaches including chemotherapy, surgery, and radiotherapy (RT) has shown promising results; however, prognosis remains poor especially in LMICs. In this article, authors have discussed the ICMR consensus guidelines on the management of EORB, including metastatic RB.
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ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.
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Laparoscopy , Neoplasms, Second Primary , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectum/pathology , Laparoscopy/methods , Neoadjuvant Therapy , Neoplasms, Second Primary/surgeryABSTRACT
Retinoblastoma (RB) is the most common intraocular tumor in childhood. It is mainly caused by mutations in both alleles of the RB1 tumor suppressor gene that is found on chromosome 13 and regulates the cell cycle. Approximately 8000 children are diagnosed with RB globally each year, with an estimated 1500 cases occurring in India. The survival rate of RB has improved to more than 90% in the developed world. Leukocoria and proptosis are the most common presenting features of RB in Asian Indian populations. Most cases of RB are diagnosed by fundus examination followed by ultrasound. The International Classification of Retinoblastoma is the most used scheme for the staging and classification of intraocular RB in India. Prenatal testing and preimplantation genetic testing for RB may be beneficial in high-risk families. Histopathologic risk factors such as massive choroidal invasion and post-laminar optic nerve help in predicting the occurrence of metastasis in children with RB, while presence of microscopic residual disease requires aggressive adjuvant treatment in eyes enucleated for group E RB. The review provides a consensus document on diagnosis and genetics of RB in India.
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We report a deep next-generation sequencing analysis of 13 sequentially obtained tumor samples, eight sequentially obtained circulating tumor DNA (ctDNA) samples and three germline DNA samples over the life history of 3 patients with triple-negative breast cancer (TNBC), 2 of whom had germline pathogenic BRCA1 mutation, to unravel tumor evolution. Tumor tissue from all timepoints and germline DNA was subjected to whole-exome sequencing (WES), custom amplicon deep sequencing (30,000X) of a WES-derived somatic mutation panel, and SNP arrays for copy-number variation (CNV), while whole transcriptome sequencing (RNA-seq) was performed only on somatic tumor.There was enrichment of homologous recombination deficiency signature in all tumors and widespread CNV, which remained largely stable over time. Somatic tumor mutation numbers varied between patients and within each patient (range: 70-216, one outlier). There was minimal mutational overlap between patients with TP53 being the sole commonly mutated gene, but there was substantial overlap in sequential samples in each patient. Each patient's tumor contained a founding ("stem") clone at diagnosis, which persisted over time, from which all other clones ("subclone") were derived ("branching evolution"), which contained mutations in well-characterized cancer-related genes like PDGFRB, ARID2, TP53 (Patient_02), TP53, BRAF, BRIP1, CSF3R (Patient_04), and TP53, APC, EZH2 (Patient_07). Including stem and subclones, tumors from all patients were polyclonal at diagnosis and during disease progression. ctDNA recapitulated most tissue-derived stem clonal and subclonal mutations while detecting some additional subclonal mutations. RNA-seq revealed a stable basal-like pattern, with most highly expressed variants belonging to stem clone. SIGNIFICANCE: In germline BRCA1 mutated and BRCA wild-type patients, TNBC shows a branching evolutionary pattern of mutations with a single founding clone, are polyclonal throughout their disease course, and have widespread copy-number aberrations. This evolutionary pattern may be associated with treatment resistance or sensitivity and could be therapeutically exploited.
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Triple Negative Breast Neoplasms , Humans , BRCA1 Protein/genetics , Disease Progression , DNA , Exome Sequencing , Triple Negative Breast Neoplasms/genetics , Germ-Line MutationABSTRACT
Background: Selective internal radiation therapy (SIRT) using a suitable ß--emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (90Y) [T1/2 = 64.2 h, Eß(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [90Y]yttria alumino silicate ([90Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20 and 36 µm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [90Y]YAS glass microspheres were administered in human patients. Results: [90Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (â¼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [90Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [90Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.
Subject(s)
Biosimilar Pharmaceuticals , Carcinoma, Hepatocellular , Embolization, Therapeutic , Liver Neoplasms , Yttrium , Rats , Animals , Humans , Microspheres , Rats, Wistar , Tissue Distribution , Cost-Benefit Analysis , Liver Neoplasms/pathology , Yttrium Radioisotopes/therapeutic use , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/drug therapy , Radiopharmaceuticals/therapeutic useABSTRACT
Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.
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Lung cancer is the most diagnosed cancer worldwide. Many non-malignant pulmonary lesions, such as tuberculosis, fungal infection, organizing pneumonia, inflammatory myofibroblastic tumor, and IgG4 disease, can mimic lung cancer due to their overlapping morphological appearance on imaging. These benign entities with minor differentiating imaging clues may go unnoticed in a high-volume cancer institution, leading to over-investigation that may result in repeated biopsies, pointless wedge resections, and related morbidities. However, with a thorough medical history, laboratory diagnostic work-up, and careful analysis of imaging findings, one can occasionally restrict the range of possible diagnoses or arrive at a definitive conclusion. When imaging features overlap, image-guided lung sampling is crucial since histopathological analysis is the gold standard.