RESUMO
BACKGROUND: Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. RESULTS: A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. CONCLUSIONS: Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).
Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Acrilamidas/uso terapêutico , Acrilamidas/efeitos adversos , Compostos de Anilina/uso terapêutico , Compostos de Anilina/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Idoso , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Quimiorradioterapia/efeitos adversos , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Indóis , PirimidinasRESUMO
BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).
Assuntos
Neoplasias Retais , Adulto , Humanos , Canal Anal/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Cuidados Pré-Operatórios , Período Pré-OperatórioRESUMO
BACKGROUND: Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer. METHODS: We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti-PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair-deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy. RESULTS: A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose-positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported. CONCLUSIONS: Mismatch repair-deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response. (Funded by the Simon and Eve Colin Foundation and others; ClinicalTrials.gov number, NCT04165772.).
Assuntos
Antineoplásicos , Segunda Neoplasia Primária , Neoplasias Retais , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Reparo de Erro de Pareamento de DNA , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Estudos Prospectivos , Neoplasias Retais/genética , Neoplasias Retais/terapia , Reto/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC. METHODS: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m2) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting. FINDINGS: Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1-52·3). Median event-free survival was not reached (95% CI 44·7 months-not reached) in the pembrolizumab group and 46·6 months (27·5-not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68-1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis). INTERPRETATION: Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Assuntos
Anticorpos Monoclonais Humanizados , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Intervalo Livre de Progressão , AdultoRESUMO
Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m2 ; UGT1A1*1*28: 65 mg/m2 ) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1-Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5-1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.
Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Irinotecano , Camptotecina , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/genética , Segunda Neoplasia Primária/etiologia , Genótipo , Quimiorradioterapia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. METHODS: A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. RESULTS: The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p = .96) or grade 2 gastrointestinal (p = .75), genitourinary (p = .44), and sexual (p = .29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p = .03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p = .005). A nonsignificant trend (p = .09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. CONCLUSIONS: Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.
Assuntos
Docetaxel , Neoplasias da Próstata , Humanos , Masculino , Docetaxel/efeitos adversos , Docetaxel/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Taxoides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Trato Gastrointestinal/efeitos da radiação , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Terapia Neoadjuvante/efeitos adversosRESUMO
INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Hospitalização , Neoplasias Pulmonares , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Feminino , Masculino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Idoso , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Terapia com Prótons/métodos , Terapia com Prótons/efeitos adversos , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Linfopenia/etiologia , Anticorpos MonoclonaisRESUMO
BACKGROUND: Standard care for non-metastatic squamous cell carcinoma of the anus (SCCA) is chemoradiotherapy, data about elderly patients are scarce. METHODS: All consecutive patients treated for non-metastatic SCCA from the French multicenter FFCD-ANABASE cohort were included. Two groups were defined according to age: elderly (≥75 years) and non-elderly (<75). RESULTS: Of 1015 patients, 202 (19.9%) were included in the elderly group; median follow-up was 35.5 months. Among the elderly, there were more women (p = 0.015); frailer patients (p < 0.001), fewer smokers (p < 0.001) and fewer HIV-infected (p < 0.001) than in the non-elderly group. Concomitant chemotherapy and inguinal irradiation were less frequent (p < 0.001 and p = 0.04). In the elderly group; 3-year overall survival (OS), recurrence-free survival (RFS) and colostomy-free survival (CFS) were 82.9%, 72.4% and 78.0%, respectively; complete response rate at 4-6 months was 70.3%. There were no differences between groups for all outcomes and toxicity. In multivariate analyses for the elderly, PS ≥ 2 and locally-advanced tumors were significantly associated with poor OS (HR = 3.4 and HR = 2.80), RFS (HR = 2.4 and HR = 3.1) and CFS (HR = 3.8 and HR = 3.0); and treatment interruption with poor RFS (HR = 1.9). CONCLUSION: In the FFCD-ANABASE cohort, age did not influence tumor and tolerance outcomes of non-metastatic SCCA. Optimal curative treatment should be offered to elderly patients.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia/efeitos adversos , Estudos Prospectivos , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown. METHODS: In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid. RESULTS: Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31-11.38) compared with no irAEs and 11.58 (95% CI, 2.11-63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8+ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration. CONCLUSIONS: The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid-treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.
Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Idoso , Pessoa de Meia-Idade , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Estudos Prospectivos , Quimiorradioterapia/efeitos adversos , Estadiamento de Neoplasias , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Idoso de 80 Anos ou mais , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. RESULTS: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03-2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). CONCLUSIONS: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.
Assuntos
Neoplasias Esofágicas , Esofagectomia , Músculo Esquelético , Terapia Neoadjuvante , Sarcopenia , Humanos , Sarcopenia/etiologia , Sarcopenia/patologia , Masculino , Feminino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/complicações , Terapia Neoadjuvante/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , Músculo Esquelético/patologia , Prognóstico , Idoso , Seguimentos , Quimiorradioterapia/mortalidade , Quimiorradioterapia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Quimiorradioterapia AdjuvanteRESUMO
OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.
Assuntos
Neoplasias do Colo do Útero , Feminino , Criança , Humanos , Neoplasias do Colo do Útero/patologia , Quimiorradioterapia/efeitos adversos , Linfonodos/patologia , Intervalo Livre de Doença , Excisão de Linfonodo , Estudos Retrospectivos , Estadiamento de Neoplasias , HisterectomiaRESUMO
BACKGROUND: To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell carcinoma (ESCC) during neoadjuvant chemoradiotherapy (nCRT). METHODS: The study included 106 ESCC patients treated with nCRT. We collected dosimetric parameters, including vertebral body volumes receiving 10-40 Gy (V10, V20, V30, V40) and EDIC and complete blood counts. Associations of the cell nadir and dosimetric parameters were examined by linear and logistic regression analysis. The receiver operating characteristic (ROC) curves were used to determine the cutoff values for the dosimetric parameters. RESULTS: During nCRT, the incidence of grade 3-4 lymphopenia, leukopenia, and neutropenia was 76.4%, 37.3%, and 37.3%, respectively. Patients with EDIC ≤ 4.63 Gy plus V10 ≤ 140.3 ml were strongly associated with lower risk of grade 3-4 lymphopenia (OR, 0.050; P < 0.001), and patients with EDIC ≤ 4.53 Gy plus V10 ≤ 100.9 ml were strongly associated with lower risk of grade 3-4 leukopenia (OR, 0.177; P = 0.011), and patients with EDIC ≤ 5.79 Gy were strongly associated with lower risk of grade 3-4 neutropenia (OR, 0.401; P = 0.031). Kaplan-Meier analysis showed that there was a significant difference among all groups for grade 3-4 lymphopenia, leukopenia, and neutropenia (P < 0.05). CONCLUSION: The dose of vertebral bone marrow irradiation and EDIC were significantly correlated with grade 3-4 leukopenia and lymphopenia, and EDIC was significantly correlated with grade 3-4 neutropenia. Reducing vertebral bone marrow irradiation and EDIC effectively reduce the incidence of HT.
Assuntos
Medula Óssea , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Medula Óssea/efeitos da radiação , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Idoso , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Adulto , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Dosagem Radioterapêutica , Leucopenia/etiologia , Neutropenia/etiologia , Linfopenia/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Endostatinas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Proteínas Recombinantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologiaRESUMO
BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.
Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Adolescente , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/prevenção & controle , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Resposta Patológica Completa , Encéfalo/patologiaRESUMO
BACKGROUND: This study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy. METHODS: In this prospective, single-center, single-arm study, we enrolled patients (18-70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48-72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3-4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2-4, time to complete radiotherapy, and safety. RESULTS: Overall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3-4 neutropenia was 28.8%, with an average duration of grade 3-4 neutropenia persistence of 3.85 days (1-7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2-4, respectively. The incidences of grade 3-4 neutropenia for cycles 1-4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41-56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient. CONCLUSION: PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.
Assuntos
Quimiorradioterapia , Fator Estimulador de Colônias de Granulócitos , Neutropenia , Polietilenoglicóis , Proteínas Recombinantes , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/terapia , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Idoso , Neutropenia/prevenção & controle , Neutropenia/etiologia , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto Jovem , Adolescente , Paclitaxel/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêuticoRESUMO
BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Cisplatino , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Feminino , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Intervalo Livre de ProgressãoRESUMO
OBJECTIVE: To investigate the application of nutritional intervention in the management of radiotherapy and chemotherapy for nasopharyngeal carcinoma. METHODS: There were 60 patients with nasopharyngeal carcinoma who were treated with chemoradiotherapy in our department from June 2020 to August 2022, including 30 subjects from the control group and 30 cases from the intervention group. RESULTS: (1) In 2002, the 3-week and 24-week NRS scores for radiotherapy and chemotherapy in the control group were higher than those in the intervention group (2.36 ± 0.85 and 1.86 ± 0.57, p = 0.014; 2.76 ± 0.77 and 2.43 ± 0.77, p = 0.023), and the difference was statistically significant (p < 0.05) (Table 2). (2) The weight of patients in the two groups after 3 wk and 24 wk of radiotherapy and chemotherapy were compared, and we found that the weights of the control group were lower than those of the intervention group (66.13 ± 5.53 and 69.03 ± 5.22, p = 0.037; 61.03 ± 5.83 and 64.93 ± 6.85, p = 0.044), and again, the difference was statistically significant (p < 0.05) (Table 3). At week 10 of chemoradiotherapy, the control group lost ≥10% of their weight in the intervention group, and severe malnutrition occurred. The control group lost ≥5% of their weight at 24 wk of chemoradiotherapy and developed malnutrition. (3) The quality of life (measured by the SF-36 scale score) after 24 wk between the two groups was compared, and the control group was lower than the intervention group in all aspects, and this difference was statistically significant (p < 0.05) (Table 4). CONCLUSION: Nutritional intervention is used in the whole management of radiotherapy and chemotherapy for nasopharyngeal carcinoma to improve patient nutritional status and quality of life.
Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Qualidade de Vida , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Quimiorradioterapia/efeitos adversos , Desnutrição/etiologiaRESUMO
Malnutrition is prevalent among patients with nasopharyngeal carcinoma undergoing radiotherapy. This study examined the nutritional status and incidence of radiation-induced oral mucositis (RIOM) in patients with nasopharyngeal carcinoma. A retrospective analysis was conducted to compare the incidence of RIOM, Nutritional Risk Screening (NRS) 2002 score, weight, body mass index (BMI), and hemoglobin levels in 338 patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) or treated with CCRT alone. The IC + CCRT group exhibited an increase in weight and BMI but a decrease in hemoglobin levels after IC compared with baseline (p < 0.001). Both groups showed differences in weight at Week 0 and BMI at Weeks 0-2 of radiotherapy (p < 0.05). The IC + CCRT group experienced an increase in NRS 2002 scores from Week 2 to Week 6 (p < 0.05). The hemoglobin levels of the IC + CCRT group were consistently lower throughout radiotherapy (p < 0.001). However, no significant difference was observed in the incidence of RIOM between the two groups (p = 0.246). Patients treated with IC + CCRT exhibited a higher nutritional risk during radiotherapy. Although the incidence of Grade III RIOM was high, no significant difference was found between the groups.
Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Estudos Retrospectivos , Estado Nutricional , Incidência , Quimiorradioterapia/efeitos adversos , Hemoglobinas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.
Assuntos
Carcinoma de Células Escamosas , Quimiorradioterapia , Neoplasias Laríngeas , Acetato de Megestrol , Neoplasias Faríngeas , Redução de Peso , Humanos , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Idoso , Acetato de Megestrol/uso terapêutico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Faríngeas/terapia , Neoplasias Faríngeas/mortalidade , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
Durvalumab is the first immune check point inhibitor that was approved for use following concurrent platinum-based chemoradiation, in patients with unresectable stage III non-small cell lung cancer. The new treatment regimen of durvalumab administered after chemoradiation resulted in higher response rates and required careful immune-related adverse effects management. We experienced a rare case of severe acute kidney injury (AKI) requiring hemodialysis after only the first dose of durvalumab, in a patient who was diagnosed with immune-related AKI by renal biopsy. Although severe (Grade 3 or more) immune-related AKI occurred in 0.9% of patients treated with durvalumab, some drugs and radiation may increase immune-related AKI. Further research is needed to identify the clinical characteristics of patients who tend to develop severe AKI so as to prevent it, by reviewing such rare cases as ours.