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1.
Oral Oncol ; 124: 105642, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34861565

RESUMO

PURPOSE: Management of clinically node-negative (N0) neck in early-stage (T1-T2) oral and/or oropharyngeal squamous cell carcinoma (OOSCC) has been controversial. The purpose of this systematic review and meta-analysis was to compare sentinel lymph node biopsy (SLNB) with elective neck dissection (END) in early-stage OOSCC. METHODS: Studies comparing SLNB versus END in early-stage clinically node-negative OOSCC were identified using validated search strategy. To be considered eligible, trials had to include patients with early-stage, clinically node-negative OOSCC who had been randomly assigned to either SLNB or END. Primary outcome of interest was overall survival (OS), while secondary outcomes included isolated neck nodal recurrence (NNR), loco-regional recurrence (LRR), and neck-shoulder function. Outcome data was pooled using random-effects model and reported as hazard ratio (HR) or risk ratio (RR) with 95% confidence interval (CI). Any p-value < 0.05 was considered statistically significant. RESULTS: A total of 608 patients from three trials comparing SLNB versus END in early-stage clinically node-negative OOSCC were included. The pooled HR of death for SLNB versus END was 1.18 (95% CI: 0.79-1.78, p = 0.41) which was not statistically significant. The rates of isolated NNR (pooled RR = 1.11, 95% CI: 0.69-1.80, p = 0.66) and LRR (pooled RR = 1.18, 95% CI: 0.81-1.72, p = 0.39) were also similar. Pooled analysis of the neck-shoulder function significantly favoured SLNB arm (pooled RR = 1.21, 95% CI: 1.12-1.32, p < 0.00001). CONCLUSION: There is low-certainty evidence that SLNB is oncologically non-inferior to END and is associated with potentially lesser functional morbidity making it an emerging alternative standard of care in patients with early-stage clinically node-negative OOSCC.

2.
Oral Oncol ; 125: 105684, 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-34963096

RESUMO

BACKGROUND: The swallowing outcomes in patients undergoing glossectomy have been inconsistently reported in the literature owing to variable follow up times, different tools for assessment and lack of single institution large scale studies. The aim of our study was to assess the patterns of swallowing outcomes over time and identify factors affecting nasogastric tube dependency at 1-year post-surgery. MATERIALS AND METHODS: This was a retrospective study of treatment naïve patients with oral tongue carcinoma who underwent surgery and attended the speech and swallow clinic between January 2016 and December 2019 at our institute were included in the study. The findings of swallowing assessment by a speech language pathologist at three time points were recorded. RESULTS: A total of 606 patients were found eligible for the study. The median age of the patients was 50 years with the 211 (34.8%) patients having T3/T4 disease. The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time with an increasing number of patients switching over to a solid diet by 1 year. A higher defect class (HR = 24.43 [3.48-171.27]) and presence of co-morbidities (HR = 4.17 [1.59-10.92]) were associated with sustained feeding tube dependency status at 1 year. A nomogram was developed based on these findings. CONCLUSION: The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time. A higher defect class and presence of co-morbidities were associated with NGT dependency at 1 year.

3.
Cancer Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786866

RESUMO

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

4.
J Surg Oncol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729779

RESUMO

BACKGROUND AND OBJECTIVES: There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. METHODS: Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. RESULTS: There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. CONCLUSION: Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.

5.
J Clin Oncol ; 39(33): 3682-3692, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34506246

RESUMO

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

6.
Rev Med Virol ; : e2276, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245622

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 continues to grow and spread throughout the world since being declared a pandemic. Despite extensive scientific research globally including repurposing of several existing drugs, there is no effective or proven therapy for this enigmatic disease which is still largely managed empirically This systematic review evaluated the role of hydroxychloroquine (HCQ) in the treatment of COVID-19 infection and was conducted using Cochrane methodology for systematic reviews of interventional studies including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to HCQ plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). A total of 10,492 patients from 19 randomised controlled trials were included. The use of HCQ was not associated with higher rates of clinical improvement (RR = 1.00, 95% CI: 0.96-1.03, p = 0.79) or reduction in all-cause mortality by Day14 (RR = 1.07, 95% CI: 0.97-1.19, p = 0.19) or Day28 (RR = 1.08, 95% CI: 0.99-1.19, p = 0.09) compared to placebo/standard of care. There was no significant difference in serious adverse events between the two arms (RR = 1.01, 95% CI: 0.85-1.19, p = 0.95). There is low-to-moderate certainty evidence that HCQ therapy is generally safe but does not reduce mortality or enhance recovery in patients with COVID-19 infection.

7.
Transfus Med ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34189780

RESUMO

BACKGROUND: Despite scientific advances, there is no effective medical therapy for coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to evaluate the safety and efficacy of convalescent plasma therapy in COVID-19. METHODS: This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to convalescent plasma plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Two reviewers independently read each preprint/publication and extracted relevant data from individual studies. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 13 206 patients from 12 randomised controlled trials were included. There was no significant difference in clinical improvement rate (RR = 1.00, 95% CI: 0.98-1.02, p = 0.96) or time to clinical improvement (median difference of 1.08 days with 95% CI ranging from -0.15 to +2.30 days) between convalescent plasma versus placebo/standard of care therapy. The use of convalescent plasma was not associated with significantly reduced risk of death (RR = 0.81, 95% CI: 0.65-1.02, p = 0.08). Reassuringly, overall incidence of infusion-related serious adverse events was low (3.25%) and not significantly different (RR = 1.14, 95% CI: 0.93-1.40, p = 0.22) for convalescent plasma transfusion compared to placebo/standard of care therapy. CONCLUSIONS: There is low to moderate certainty evidence that the addition of convalescent plasma to current standard of care therapy is generally safe but, does not result in any significant clinical benefit or reduction of mortality in COVID-19.

8.
Clin Lymphoma Myeloma Leuk ; 21(8): 497-507, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33947632

RESUMO

This review aimed to assess diagnostic performance of 18F-flouro-deoxy-glucose positron emission tomography (FDG-PET) with or without computed tomography (CT) scan in primary central nervous system lymphoma (PCNSL). Eligible studies reporting diagnostic accuracy of pretreatment FDG-PET(CT) scan in immunocompetent adults with PCNSL were identified through systematic literature search. Data on diagnostic performance from individual studies was summarized in a 2 × 2 table classifying patients as true positives, true negatives, false positives, and false negatives using histopathologic diagnosis as reference standard. Random-effects model was used to calculate weighted-mean pooled sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio with 95% confidence intervals (95% CI). Twenty-nine primary studies involving 967 patients were included. Weighted-mean pooled sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio was 87% (95% CI, 83%-90%), 85% (95% CI, 81%-88%), 84% (95% CI, 81%-88%), 87% (95% CI, 84%-90%), and 29.78 (95% CI, 18.34-48.35), respectively, demonstrating acceptably high diagnostic accuracy of pretreatment FDG-PET(CT) scan in immunocompetent patients with PCNSL.

9.
Head Neck ; 43(7): 2032-2044, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33751711

RESUMO

BACKGROUND: To examine the molecular profiles of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas (HNSCCs), expression of epidermal growth factor receptor (EGFR), phospho-EGFR dimers, hypoxia markers, and cancer stem cell markers were evaluated. METHODS: HPV-status was confirmed using RNA-ISH. Immunohistochemical data of biomarker expression levels were analyzed using the Mann-Whitney U test. The clinical outcomes and biomarker expression in the HPV-positive (n = 25), matched HPV-negative (n = 49), and p16-positive/HPV-negative (n = 20) subgroups were comparatively analyzed. RESULTS: HPV was detected in 25 (5.8%) cases and was significantly associated with favorable outcomes. HPV-positive tumors exhibited lower membrane expression of EGFR, pEGFRY1068, pEGFRY1173, CD44, CD44v6, and CD98hc than HPV-negative and p16-positive tumors. The expression of HIF1α, CA9, ALDH1A1, and SOX2 was not significantly associated with HPV-status. The clinical outcomes and biomarker expression levels were similar between the HPV-negative and p16-positive HNSCC. CONCLUSION: HPV-positive HNSCC exhibited distinct molecular profile compared to HPV-negative and p16-positive HNSCC. The clinical and molecular profiles were similar between p16-positive and HPV-negative subgroups.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Carcinoma de Células Escamosas/genética , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias de Cabeça e Pescoço/genética , Humanos , Papillomaviridae/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
10.
Asian Pac J Cancer Prev ; 22(3): 793-800, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773543

RESUMO

BACKGROUND: Cancer treatment during nationwide lockdown due to the COVID-19 pandemic has posed several challenges in the delivery of cancer care and carries tremendous potential sequel of impoverishing the households. This study aims to examine the economic distress faced by breast cancer patients receiving treatment at Tata Memorial Center (TMC) Mumbai, India during the nationwide lockdown initiated in March 2020 following the outbreak of COVID-19. METHODS: A total of 138 non-metastatic breast cancer patients who were accrued in this study at TMC before imposing of lockdown, and their treatment was impacted because of the COVID-19 outbreak, were interviewed. Telephonic interviews were conducted using a structured schedule which contained information on household and demographic characteristics of the patients, knowledge about COVID-19, their daily expenditure for treatment, difficulties faced during lockdown and how they met expenditures. Descriptive statistics and logistic regression were used in the analyses. RESULTS: The average monthly expenditure of cancer patients had increased by 32% during the COVID-19 period while the mean monthly household income was reduced by a quarter. More than two-thirds of the patients had no income during the lockdown. More than half of the patients met their expenditure by borrowing money, 30% of the patients used their savings, 28% got charity and 25% used household income. About 81% of the patients had reported shortage of money, 32%  reported shortage of food and 28% reported shortage of medicine. The distress financing was significantly higher among patients receiving treatment in Mumbai compared to those receiving treatment at their native cities (67% vs. 46%), patients under 40 years of age, illiterate, currently married, Muslim and staying at a rented house. CONCLUSION: The incremental expenditure coupled with reduced or no income due to the closure of economic activities in the country imposed severe financial stress on breast cancer patients.


Assuntos
Neoplasias da Mama/economia , COVID-19 , Efeitos Psicossociais da Doença , Estresse Financeiro , Financiamento Pessoal , Gastos em Saúde , Adulto , Fatores Etários , Neoplasias da Mama/terapia , Estudos de Coortes , Controle de Doenças Transmissíveis , Feminino , Geografia , Humanos , Renda , Índia , Alfabetização , Estado Civil , Pessoa de Meia-Idade , Religião , SARS-CoV-2
11.
Bone Marrow Transplant ; 56(7): 1558-1562, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33514924

RESUMO

Transplant associated thrombotic microangiopathy (TA-TMA) is life-threatening complication post allogeneic stem cell transplant (ASCT). Risk factors and prognosis of TA-TMA are not well defined. We retrospectively studied consecutive ASCT patients with AML, ALL, and CML from January 2008 to March 2019 to study the incidence, risk factors, and outcomes of TMA. Definitive and probable TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and Cho criteria, respectively. Risk factors explored were age, gender, diagnosis, type of transplant, use of tyrosine kinase inhibitors (TKI) pre transplant, conditioning regimen, and acute GVHD. Standard statistical methods were used. Total 241 patients, 179 (74.2 %) males, median age of 29 years were studied. Diagnoses were AML in 104, ALL in 85 (Ph+ve 23) and CML 52. Total 26 (10.7%) patients (22 males) developed TA-TMA at median of day+102. On multivariate analysis, pre-HSCT TKI (OR 2.7, p = 0.028), haplo-HSCT (OR 3.16, p = 0.018) and presence of acute GVHD (OR 4.17, p = 0.003) were significant risk factors. With a median follow up of 60 months, median OS with and without TA-TMA was 18 and 97 months respectively (p = 0.021). The association of pre-HSCT with TKI with TA-TMA merits further exploration in prospective studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia
12.
J Clin Oncol ; 39(11): 1234-1242, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33497252

RESUMO

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; P < .0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P = .002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P = .83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P = .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.


Assuntos
Pelve/efeitos da radiação , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Fatores de Risco , Resultado do Tratamento
13.
Oral Oncol ; 114: 105078, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33183996

RESUMO

We recruited 69 consecutive patients with oral cavity squamous cell carcinoma (OSCC) between January 2017 and January 2019 for this study. All patients underwent up-front surgery followed by adjuvant radio- and/or chemotherapy as indicated. Pre-operative serum levels of C-reactive protein (CRP) and cell-free chromatin (cfCh) were estimated by ELISA and post-operative histopathological features were recorded. CRP levels were significantly associated with poor histopathological features, advanced stage, bone erosion, extracapsular spread and pathological nodal status. CRP levels were not associated with survival. CfCh levels were significantly associated with bone erosion and neck nodes and patients with higher cfCh levels had significantly poor overall survival.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/sangue , Cromatina/metabolismo , Neoplasias Bucais/sangue , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Masculino , Neoplasias Bucais/mortalidade
14.
Int J Hematol ; 112(6): 835-840, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876851

RESUMO

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m2 on day 1, 4, 8 and 11, cyclophosphamide 1 g/m2 on day 8 and 9, and GCSF 10 µg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m2 on day 1 and day 2 followed by GCSF 10 µg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 106/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 106/kg (0.4-24.2). Target CD34 cells yield of 5 × 106/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.


Assuntos
Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Filgrastim/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
15.
Br J Cancer ; 123(12): 1757-1766, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32939054

RESUMO

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42-0.93)], LRC [HR (95% CI) = 0.56 (0.37-0.86)] and OS [HR (95% CI) = 0.63 (0.43-0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37-0.82), LRC:HR (95% CI) = 0.55 (0.36-0.85) and OS:HR (95% CI) = 0.54 (0.36-0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008). CONCLUSIONS: High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Núcleo Celular/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Adulto , Idoso , Alphapapillomavirus/isolamento & purificação , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Dosagem de Genes , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Radiossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto Jovem
16.
JAMA Netw Open ; 3(8): e2011777, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32833018

RESUMO

Importance: The optimum duration of adjuvant trastuzumab among patients with early breast cancer is uncertain but of great therapeutic relevance. Objective: To compare shorter durations with 1 year of adjuvant trastuzumab for patients with early breast cancer. Data Sources: PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings were searched from January 1, 2005, to June 30, 2019, for relevant randomized clinical trials (RCTs). Study Selection: To be eligible, the trial had to be randomized, compare a shorter duration with 1 year of trastuzumab as adjuvant treatment, and include patients with early breast cancer. Data Extraction and Synthesis: Individual patient data for disease-free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed. The DFS and OS hazard ratios (HRs) were estimated from the reconstructed survival curves as well as published estimates. The HR for DFS was used to test noninferiority using the median noninferiority margin of eligible RCTs. This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: The primary outcome was DFS; OS and cardiac toxic effects were secondary outcomes. Results: There were 6 eligible RCTs with a median DFS noninferiority margin of 1.3 (range, 1.15-1.53), 5 of which had extractable individual patient data for 11 376 patients, 1659 DFS events, and 871 deaths. For shorter duration vs 1 year of trastuzumab, the 5-year DFS was 85.42% (95% CI, 84.41%-86.38%) vs 87.12% (95% CI, 86.15%-88.02%) (HR, 1.14; 95% CI, 1.03-1.25, 1-sided P for noninferiority = .004), and OS was 92.39% (95% CI, 91.61%-93.10%) vs 93.46% (95% CI, 92.73%-94.13%) (HR, 1.17; 95% CI, 1.02-1.33). Using trial-level published estimates from 6 RCTs, including 11 603 patients, 1760 DFS events, and 930 deaths, the HR for DFS was 1.15 (95% CI, 1.04-1.26; 1-sided P for noninferiority = .002) and, for OS, 1.17 (95% CI, 1.03-1.33). There was significantly less risk of congestive heart failure with shorter-duration trastuzumab (relative risk, 0.53; 95% CI, 0.38-0.74). Conclusions and Relevance: In this study, a shorter duration of adjuvant trastuzumab was noninferior to its 1-year administration and resulted in lower rates of cardiac toxic effects. These results suggest that a shorter duration may be the preferred option for patients with low-risk disease or a predisposition to cardiac toxic effects.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Trastuzumab/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , Resultado do Tratamento
17.
Clin Lymphoma Myeloma Leuk ; 20(11): e836-e845, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32712087

RESUMO

The extent of staging required to evaluate for systemic involvement in patients with primary central nervous system lymphoma (PCNSL) remains controversial. Eligible studies reporting on diagnostic yield of extensive systemic staging, including pre-treatment whole-body 18F-fluoro-deoxy-glocose positron emission tomography with or without computed tomography, in immuno-competent adults with PCNSL were identified through systematic literature search. Diagnostic yield was defined as the proportion of patients with abnormal test results outside the neuraxis that led to detection of concordant systemic high-grade lymphoma on an individual patient basis (true positives). Data were pooled using random-effects model to produce summary estimates with 95% confidence intervals (CIs). Weighted-mean pooled analysis involving 1099 patients from 14 primary studies provided an overall diagnostic yield of 6% (95% CI, 4%-8%) for extensive systemic staging in PCNSL with implications for diagnosis, prognosis, and therapy. Summary estimates of false positivity were just marginally lower at 5% (95% CI, 3%-8%) for such systemic staging.

18.
J Oral Pathol Med ; 49(9): 876-885, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32512627

RESUMO

BACKGROUND: The present study aims to comprehensively analyze expression of Activin signaling components in oral cancer and to determine the predominant Activin expressed and its influence on prognosis. As our preliminary studies indicated regulation of Activin gene by p63, we also propose to assess its correlation with p63/p53 in oral tumors and its impact on outcome. METHODS: Expression of Activin subunits, receptors, and regulators was assessed by qRT-PCR and Western blotting. Correlation between Activin A and p63/p53 expression was evaluated in oral tumors by immunohistochemistry and their association with clinical outcome was determined by Kaplan-Meier curves and Cox regression. RESULTS: Activin ßA transcripts were upregulated (P = .013) in oral dysplastic and cancer cells compared with normal oral mucosa. Expression of Activin receptors and regulators was also altered. Activin ßA protein was significantly upregulated in oral tumors and adjacent normal tissues compared with normal oral mucosa (P < .0001). Expression of Activin ßA and p63 significantly correlated in oral tumors, correlation being stronger in tumors with high p53 (r = -.394, P = .005). Activin ßA overexpression was associated with advanced tumor stage (P = .021), positive nodes (P = .045), poor recurrence-free survival (P = .013), and overall survival (P = .024), while its concomitant overexpression with p63 was a better predictor of recurrence-free survival (HR = 10.66, CI: 1.41-80.19). CONCLUSIONS: Activin A overexpression is an early event in oral cancer pathogenesis and can independently predict survival. Moreover, in combination with p63 overexpression, it served as a better marker for poor prognosis. Activin A could thus be a promising target for improved outcome in oral cancer patients.


Assuntos
Ativinas , Proteínas de Membrana , Neoplasias Bucais , Ativinas/genética , Humanos , Subunidades beta de Inibinas/genética , Neoplasias Bucais/genética
19.
Eur J Clin Pharmacol ; 76(10): 1427-1436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32529316

RESUMO

PURPOSE: Patients of non-small cell lung cancer (NSCLC) with brain metastases have limited treatment options. High-dose erlotinib (HDE) and gefitinib (HDG) have been tried in the past. This study investigates the cerebrospinal fluid (CSF) disposition and safety of both, high-dose erlotinib and gefitinib regimens. METHODS: Eleven and nine patients were treated with erlotinib and gefitinib, respectively. All patients received 1 week of standard dose of erlotinib (150 mg OD) or gefitinib (250 mg OD), followed by the high dose (1500 mg weekly for erlotinib and 1250 mg OD for gefitinib) from day 8. Blood and CSF samples were collected on days 7 and 15, 4 h after the morning dose and drug levels determined using LC-MS/MS. Adverse events were documented as per CTCAE 4.03 till day 15. RESULTS: Pulsatile HDE and daily HDG resulted in 1.4- and 1.9-fold increase in CSF levels, respectively. A constant 2% CSF penetration rate was observed across both doses of erlotinib, while for gefitinib the penetration rate for high dose was half that of the standard dose suggesting a nonlinear disposition. Three patients on HDE treatment discontinued treatment after the first dose due to intolerable toxicities, whereas HDG was better tolerated with no treatment discontinuations. Since CSF disposition of gefitinib followed saturable kinetics, a lower dose of 750 mg was found to achieve CSF concentrations comparable to that of the 1250 mg dose. CONCLUSIONS: HDG was better tolerated than HDE. CSF disposition of gefitinib was found to be saturable at a higher dose. Based on these findings, the dose of 750 mg OD should be considered for further evaluation in this setting.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Gefitinibe/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cromatografia Líquida , Relação Dose-Resposta a Droga , Cloridrato de Erlotinib/efeitos adversos , Cloridrato de Erlotinib/farmacocinética , Feminino , Gefitinibe/efeitos adversos , Gefitinibe/farmacocinética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem
20.
Br J Radiol ; 93(1109): 20190857, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101463

RESUMO

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, (p = 0.006), kurtosis ≥4.18; p = 0.019, skewness ≤-0.59, p = 0.001, and standard deviation ≥43.18; p = 0.009). Inferior local control was associated with medium filtered features entropy ≥4.54; p 0.01 and skewness ≤ - 0.12; p = 0.02. Using fine filters, entropy ≥4.29 and kurtosis ≥-0.27 were also associated with inferior local control (p = 0.01 for both parameters). Multivariate analysis showed medium filter entropy as an independent predictor for LFS and local control (p < 0.001 & p = 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.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias Laríngeas/mortalidade , Laringectomia/mortalidade , Neoplasias Faríngeas/mortalidade , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/diagnóstico por imagem , Neoplasias Faríngeas/cirurgia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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