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BACKGROUND: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. METHODS: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). RESULTS: A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. CONCLUSIONS: In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Adjuvantes Imunológicos/uso terapêutico , Administração Intravenosa , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/administração & dosagem , Antígeno B7-H1/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
INTRODUCTION: Children ≤5 years of age with Ewing's sarcoma (ES) possibly have a distinct disease biology, data on which are scarce. We evaluated clinical features, outcomes, and prognostic factors of ES among children with age ≤5 years. METHODS: Children with ES registered between 2003 and 2019 were included. Baseline clinical and treatment details were retrieved from medical records. Prognostic factors were identified using multivariable Cox regression. Clinical features and outcomes of children ≤5 years were compared with those greater than 5 years by chi-square and log-rank tests. Propensity score-matched (PSM) analysis was done to evaluate the impact of age on survival in the metastatic and localized subgroups. RESULTS: Out of the 859 patients, 86 (10%) were ≤5 years of age (median age 4 years, 60 males [69.8%]). The most common location was the extremities (37.2%), followed by thorax (27.9%) and head and neck (H&N) (22.1%); baseline metastases were seen in 25 patients (29.8%). The median event-free-survival (EFS) and overall survival (OS) were 25.6 and 68.7 months, respectively. Metastatic disease predicted inferior OS (hazard ratio [HR] = 2.54, p = .018) and EFS (HR = 2.47, p = .007], symptom duration ≤3 months predicted an inferior OS (HR = 2.17, p = .048). Compared to age greater than 5 years, younger children had more H&N and less pelvic primaries (p < .001) and lesser baseline metastases (p = .037). PSM analysis did not reveal any significant impact of age on OS in the metastatic (HR = 1.59, p = .29) or localized cohort (HR = 1.77, p = .09). CONCLUSIONS: Children with ES ≤5 years of age have a distinct favorable clinical presentation. However, age is not an independent prognostic factor for survival outcomes when adjusted for confounders.
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The role of neoadjuvant chemotherapy (NACT) in eyelid and orbital malignancies is not well defined. It has been tried with good success in cases of eyelid sebaceous gland carcinoma but there is very limited literature on its role in cases of ocular surface squamous neoplasia. A 54-year-old man presented with gradually increasing swelling of the right upper eyelid for the past 2 years. On examination, a large friable papillary mass was found covering the entire conjunctival surface (T3N0M0). Incisional biopsy from the mass was suggestive of papillary squamous cell carcinoma. There was no lymph node or distant metastasis as confirmed by whole-body positron emission tomography-CT scan. A trial of NACT (3 cycles of paclitaxel and cisplatin) was given and the mass shrunk in size considerably making it amenable to surgical resection. The conjunctival surface healed completely and there was no recurrence at 1 year of follow up. NACT can be tried in unresectable large ocular surface neoplasia to make the tumor more amenable to surgical resection.
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Carcinoma de Células Escamosas , Neoplasias Oculares , Neoplasias Palpebrais , Neoplasias das Glândulas Sebáceas , Masculino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Túnica Conjuntiva/patologia , Neoplasias Palpebrais/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias das Glândulas Sebáceas/patologiaRESUMO
Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003-2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases.
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Neoplasias Ósseas , Hipoalbuminemia , Sarcoma de Ewing , Humanos , Masculino , Feminino , Criança , Adolescente , Sarcoma de Ewing/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Resultado do Tratamento , Neoplasias Ósseas/tratamento farmacológicoRESUMO
BACKGROUND: Diagnostic delays in cancers are frequent in developing countries due to poor health infrastructure. Existing literature from developed countries suggests that diagnostic interval in bone sarcomas is primarily dictated by tumour biology with no impact on survival. This study evaluates the social and biological determinants of the diagnostic interval in bone sarcomas in a resource-challenged setting and assesses its impact on treatment outcomes. METHODS: A retrospective single-institutional study was conducted on patients with high-grade bone sarcomas recorded in the sarcoma clinic database between 2003 and 2018. Baseline clinical characteristics and treatment outcomes were recorded. Logistic regression was performed to assess the impact of baseline clinical and social characteristics (distance from treating centre and rural vs. urban residence) on the diagnostic interval. Further, the impact of diagnostic interval on histologic response to neoadjuvant chemotherapy, amputation requirement in extremity sarcomas and survival was evaluated. RESULTS: A total of 1227 patients were included for analysis. The median diagnostic interval was 4 months (3-7 months). Age above 18 years, Ewing sarcoma (ES) diagnosis, absence of fever at presentation and tumour size above 7.5 cm were predictors of a longer diagnostic interval (>4 months). The length of the diagnostic interval did not impact amputation requirement or survival outcomes. However, the proportion of patients with good necrosis post-neoadjuvant chemotherapy was lower among patients with longer diagnostic intervals (25% vs. 34·16%; p-value = .04). CONCLUSION: Tumour characteristics rather than social factors determined the diagnostic interval. Diagnostic interval did not impact survival outcomes even in a resource-constrained setting.
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Neoplasias Ósseas , Osteossarcoma , Sarcoma de Ewing , Sarcoma , Humanos , Adolescente , Estudos Retrospectivos , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Sarcoma/patologiaRESUMO
INTRODUCTION: Soft tissue sarcoma(STS) is a rare and heterogeneous group of disorders with dismal outcomes in metastatic setting. Pazopanib and oral metronomic chemotherapy (OMT) have been evaluated as therapeutic options in this cohort. MATERIALS AND METHODS: We conducted a retrospective, single center study evaluating 45 patients with unresectable and/or metastatic STS, who received pazopanib or oral metronomic regimen as per instituitonal protocol between January 2013 and December 2019. An informal cost minimisation analysis was conducted for both OMT and pazopanib arms, considering equivalent outcomes for both (PFS and OS). RESULTS: Median PFS in OMT and Pazopanib groups was 4.13 months and 3.53 months,respectively (HR1.31, 95% CI:0.68-2.51, p = 0.41) Only one patient in the OMT group achieved an objective response (partial response) and no objective response was noted in the pazopanib group. The incidence of grade III/IVtoxicities was higher with pazopanib than with OMT (p = 0.08). There were no toxicity related deaths noted in either arm. CONCLUSIONS: Our study demonstrates that OMT have a similar progression free survival (PFS) and overall survival (OS) in metastatic STS. This study raises the possibility that OMT might be an equally efficacious and less toxic alternative to pazopanib, without compromising survival outcome especially in LMIC.
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Sarcoma , Neoplasias de Tecidos Moles , Análise Custo-Benefício , Humanos , Indazóis , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , SulfonamidasRESUMO
BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48-11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
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Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indazóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , África do Norte , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Ásia , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Neoplasias Renais/etnologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Oriente Médio , Intervalo Livre de Progressão , Estudos Prospectivos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Fatores de Risco , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Background: . Seminomatous germ cell tumour (SGCT) is a rare but curable malignancy of young adults. The literature on management and outcome of SGCT is scarce from India. We report the demography and treatment outcome of SGCT at our centre. Methods: . We did a retrospective analysis of patients with SGCT treated from March 2011 to December 2018. Patients were staged appropriately with imaging, and pre- and postoperative tumour markers. High inguinal orchiectomy was performed in all with a testicular primary and received subsequent stage-adjusted adjuvant treatment. Patients were monitored for metabolic syndrome during follow-up after completion of treatment. Results: . We treated 85 patients with a median age of 37 (range 20-68) years. The primary site of the tumour was the testis in 80 (94%) and mediastinum in 5 (6%) patients. Cryptorchidism was present in 20 (25%) patients and testicular violation was present in 11 (14%) patients. Stage of the disease was I in 61, II in 13 and III in 6 patients. Adjuvant treatment in stage I disease was single-agent carbo-platin (area under the curve ×7) in 38 (62%), surveillance in 20 (33%) and radiotherapy in 3 (5%) patients. Five patients in the surveillance group relapsed. The 7-year mean (SD) relapse-free survival and overall survival were 83.1% (8%) and 98.7% (1.3%), respectively. Thirty-one patients (n = 52, 60%) had features of metabolic syndrome. Conclusions: . SGCTs have a high cure rate. Long-term follow-up is essential for monitoring toxic effects. Early diagnosis, avoidance of testicular violation and multidisciplinary management are the key features for better long-term outcome in SGCT.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias Testiculares/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Data on patients with localized Ewing sarcoma family of tumors (ESFT) who have received a uniform chemotherapy protocol are minimal. METHODS: This is a single institutional review of patients with ESFT treated between June 2003 and November 2011. RESULTS: 224/374 (60%) patients with ESFT presented with localized disease; median age was 15 years (range: 0.1-55). Ninety-nine patients underwent surgery of which 50 received adjuvant radiotherapy; 80 patients received radical radiotherapy following neoadjuvant chemotherapy. At median follow-up of 40.2 months (range: 1.3-129), 5-year EFS, OS, and local-control-rate, were 36.8 ± 3.6%, 52.4 ± 4.3%, and 63 ± 4.3%, respectively. In multivariate analysis, tumor diameter > 8 cm (P = 0.03), symptom duration > 4 months (P = 0.04), and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior EFS; spine/abdomino-pelvic primary (P = 0.009) and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior OS. Tumor size > 8 cm (P = 0.03) and radical radiotherapy as local treatment (P = 0.01) predicted inferior local-control-rate. CONCLUSION: Prognostic hazard models for EFS and OS based on significant prognostic factors suggested that patients with combination of ESFT of spine/abdomino-pelvic region and baseline WBC > 11 × 10(9) /L had inferior OS (hazard ratio 4.44, P < 0.001) while patients with combination of ESFT with symptom duration > 4 months, tumor diameter > 8 m and baseline WBC > 11 × 10(9) /L had inferior EFS (hazard ratio 3.89, P = 0.002).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Adolescente , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Contagem de Leucócitos , Masculino , Terapia Neoadjuvante , Prognóstico , Radioterapia Adjuvante , Sarcoma de Ewing/patologia , Vincristina/administração & dosagemRESUMO
BACKGROUND: Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. RESULTS: Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. CONCLUSIONS: This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.
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Antieméticos/uso terapêutico , Dexametasona/efeitos adversos , Morfolinas/uso terapêutico , Náusea/prevenção & controle , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Ondansetron/efeitos adversos , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/prevenção & controle , Administração Intravenosa , Adolescente , Anti-Inflamatórios/uso terapêutico , Aprepitanto , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Masculino , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Ondansetron/administração & dosagem , Ondansetron/uso terapêutico , Ontário , Indução de Remissão , Vômito/induzido quimicamenteRESUMO
BACKGROUND: Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy protocol are minimal. We aimed to examine this aspect in our patients, identify prognostic factors and compare the same with osseous Ewing sarcoma. PROCEDURES: A single institutional data review of patients with EES treated between June 2003 and November 2011 with uniform chemotherapy and evaluated on intent-to-treat analysis was done. RESULTS: Of 374 patients with Ewing sarcoma, 60 (16%) were EES with median age 16 years; 20 (33%) had metastases. After median follow-up of 25 months (range: 1.7-104.4), 5-year event free survival (EFS), OS, and local-control-rate were 47.1 ± 7.9%, 61.6 ± 7.8%, and 77.9 ± 8.6%, respectively for entire EES cohort. In multivariate analysis, hemoglobin ≤ 10 g/dl (P = 0.03), and white blood cell count (WBC) >11 × 10(9) /L (P = 0.009) predicted inferior EFS for the entire EES cohort. Low hemoglobin (P = 0.05) and high LDH (P = 0.01) predicted inferior OS for the entire EES cohort on multivariate analysis. As compared to the cohort of skeletal primary (n = 314), higher proportion of patients underwent surgery in the cohort of EES (P = .003); EFS (P = 0.004) and OS (P = 0.08) were superior for patients with EES than patients with skeletal Ewing sarcoma. CONCLUSION: These data of EES suggests that low hemoglobin and high WBC count adversely affect EFS. Overall outcome was significantly better for EES than skeletal primary tumors.
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Sarcoma de Ewing/mortalidade , Adolescente , Quimioterapia Adjuvante , Feminino , Humanos , Contagem de Leucócitos , Masculino , Análise Multivariada , Prognóstico , Sarcoma de Ewing/secundário , Sarcoma de Ewing/terapia , Resultado do TratamentoRESUMO
Pessaries are a viable alternative to the surgical management of prolapse. Occasional cases of vesicovaginal fistula, rectovaginal fistula, erosion and subsequent impaction have been reported. Fallopian tube prolapse has rarely been reported post hysterectomy, but neither with pessary use nor with an intact uterus. We report a case of prolapsed fallopian tube subsequent to a neglected pessary, presenting as vaginal bleeding, with a coincidental asymptomatic endometrial polyp which was picked up by chance. Women with tubal prolapse may be asymptomatic and observation alone might lead to resolution as evident in our case.
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Doenças das Tubas Uterinas/diagnóstico , Doenças das Tubas Uterinas/etiologia , Pessários/efeitos adversos , Hemorragia Uterina/etiologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Prolapso , VaginaRESUMO
Background: Lorlatinib, an anaplastic lymphoma kinase (ALK)-inhibitor, is approved as frontline as well as subsequent line of therapy in ALK-rearranged advanced non-small cell lung cancer (NSCLC). There is limited literature about safety and efficacy of lorlatinib in Indian patients. Materials and methods: This was a retrospective multicentre study on patients with ALK-rearranged advanced NSCLC received lorlatinib as second line and beyond between May 2017 and December 2021. ALK was tested either by immunohistochemistry or fluorescent in-situ hybridisation. Clinicopathologic features, treatment details, toxicity and outcomes were analysed. Results: A total of 38 patients were enrolled with a median age of 54 years (range: 30-72) and male: female ratio of 20:18. Fifteen (44%) patients had brain metastases at baseline. Lorlatinib use was - second line in 11 (29%), third line in 21 (55%) and fourth line in 4 (11%) of patients, respectively. The best radiologic response to lorlatinib was - complete response in 9 (24%), partial response in 17 (46%), stable disease in 9 (24%) and progressive disease in 2 (5%) of patients, respectively. After a median follow-up of 76.6 months (95% CI: 68.9-100), the median progression-free survival (PFS) of lorlatinib was not reached (95% CI: 24.3-not reached) and median overall survival (OS) of the whole cohort was 93.1 months (95% CI: 62-not reached). Both median PFS (p = 0.48) and median OS (p = 0.74) was similar between second line and later line use of lorlatinib. Thirty-three (87%) patients experienced treatment-related toxicity and six (16%) patients required dose modification. Conclusion: Lorlatinib was highly efficacious in terms of overall response rate, median PFS and median OS in this small real-world cohort of advanced ALK+ve NSCLC with a manageable safety profile.
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Background Treatment of metastatic renal cell cancer (mRCC) has revolutionized with the introduction of anti-VEGF tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). There is limited data in the literature on the outcomes of Indian patients treated with TKI. Here, we report the outcome of mRCC treated with first-line TKI in a resource-poor setting. Material and methods This is a single-center retrospective study of clear cell mRCC treated with first-line TKI from June 2012 to December 2022. Demographic characteristics and treatment details, including outcome data, were captured from electronic medical records. Patients who received at least one week of therapy were eligible for survival analysis. Results A total of 345 patients with metastatic clear cell histology were analyzed, with a median age of 61 years (range: 20-84 years). One hundred and eighty patients (52%) underwent nephrectomy before systemic therapy. The majority received pazopanib (257 patients, 75%), followed by sunitinib (36 patients, 10%) and cabozantinib (21 patients, 6%); 145 (45%) patients required dose interruption, and 143 (43%) required dose modification of TKI for adverse events. After a median follow-up of 44 months, the median progression-free survival (PFS) was 20.3 months (95% CI: 17.8-24.8), and the median overall survival (OS) was 22.7 months (95% CI: 18.8-28.3). In the poor-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS in multivariate analysis. Conclusion This is the largest single-center cohort of clear cell mRCC from Asia. Median PFS was 20.3 months with predominantly TKI monotherapy. In the poor-risk IMDC group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS.
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Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty-eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5-33); 31 (65%) had metastases. After median follow-up of 20.4 months (range: 1.3-64.9), 3-year EFS, OS, and local-control-rate were 13.5 ± 5.5%, 15.4 ± 9%, and 41.3 ± 14.9%, respectively. Hypoalbuminemia (≤3.4 g/dl) predicted inferior EFS and OS for both entire cohort and metastatic group. All patients with hypoalbuminemia (n = 10) had low BMI as compared to 23/38 without hypoalbuminemia (P = 0.02).
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Hipoalbuminemia/mortalidade , Tumores Neuroectodérmicos Primitivos Periféricos/mortalidade , Neoplasias Pélvicas/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/patologia , Hipoalbuminemia/terapia , Lactente , Masculino , Metástase Neoplásica , Tumores Neuroectodérmicos Primitivos Periféricos/sangue , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Tumores Neuroectodérmicos Primitivos Periféricos/terapia , Neoplasias Pélvicas/sangue , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/terapia , Taxa de SobrevidaRESUMO
Though there is no definite agreement on diagnostic criteria or definition of chronic ectopic pregnancy (CEP), it could be deemed to be a variant of pregnancy of unknown location with non-specific clinical signs and symptoms. This was a case of a para 2+2 who presented with lower abdominal pain and bleeding per vaginum, and initial ultrasound was suggestive of a tubo-ovarian abscess/mass. With a further MRI scan and a diagnostic laparoscopy, she was found to have a CEP and had a laparoscopic salpingectomy for management. The diagnosis of CEP could be quite challenging as a result of the protracted symptoms, often negative/low serum B-HCG and ultrasound features mimicking a pelvic mass. A high index of suspicion is needed, and an MRI scan and diagnostic laparoscopy often aid in diagnosis and management.
Assuntos
Abscesso Abdominal , Laparoscopia , Ooforite , Gravidez Ectópica , Salpingite , Gravidez , Feminino , Humanos , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/cirurgia , Ooforite/cirurgia , Salpingite/cirurgia , Abscesso Abdominal/cirurgiaRESUMO
The most common oncogenic driver in non-small-cell lung cancer (NSCLC) is the epidermal growth factor receptor (EGFR) gene mutations that occur more frequently among Asians (30%-50%) as opposed to Caucasians (10%-15%). Lung cancer is one of the most prevalent cancers in India, with a reported adenocarcinoma positivity ranging between 26.1% and 86.9% in NSCLC patients. The prevalence of EGFR mutations in adenocarcinoma patients (36.9%) in India is higher than that of Caucasian patients and lower than that of East Asian patients. The exon 19 deletion (Ex19del) is more common than exon 21 L858R mutations in Indian patients with NSCLC. Studies have shown that the clinical behaviour of patients with advanced NSCLC differs between EGFR Ex19del and exon 21 L858R mutation status. In this study, we investigated the differences in clinicopathological features and survival outcomes after first line and second-line treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs) in NSCLC patients with Ex19del and exon 21 L858R EGFR mutation status. This study also focuses on the role and potential benefits of dacomitinib, a second-generation irreversible EGFR TKI, in patients with Ex19del and exon 21 L858R EGFR mutation-positive advanced NSCLC in Indian settings.
Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Éxons/genéticaRESUMO
AIM: Data on occurrence of pneumothorax after the use of oral pazopanib in advanced soft tissue sarcoma (STS) with lung metastases are scarce in literature. We aimed to evaluate those in our patients. METHODS: This was a single center retrospective study of incidence of pneumothorax in patients with lung metastases in advanced STS treated with oral pazopanib between July, 2016 and December, 2020. Patients were treated with pazopanib usually from 2nd line onwards with a dose ranging from 400 mg to 800 mg once daily. RESULTS: Total of 34 patients with lung metastasis in a setting of advanced STS were treated with oral pazopanib during the study period. The setting of pazopanib use was 2nd line in four and 1st line in one of them. The starting dose was 600 mg once daily in three patients, 400 mg OD in one patient, and 800 mg OD in one patient. Five patients developed pneumothorax with duration on pazopanib of 6, 7, 24, 6, and 2.5 months, respectively. Three patients had symptoms and required chest tube drainage. None of them were smokers or had any other underlying lung disease. The disease response of those patients was stable disease in four and partial response in one during treatment with pazopanib. One patient had a rechallenge with further pazopanib course without any recurrence of pneumothorax. CONCLUSIONS: Pneumothorax is a rare pulmonary complication after pazopanib use in patients with lung metastasis. Clinicians should be aware of this rare complication as literature is scarce. Rechallenge with pazopanib is feasible after pneumothorax.