Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study.

PURPOSE: Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS: We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS: Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS: Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.

Oncological Surgery During the COVID-19 Pandemic: Effectiveness of Preoperative Screening and Factors Associated with Postoperative SARS-CoV-2 Infection.

BACKGROUND: Routine preoperative screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with reverse transcriptase-polymerase chain reaction (RT-PCR) may reduce in-hospital SARS-CoV-2 transmission. METHODS: This was a prospective, observational, cohort study. The endpoints were the incidence of asymptomatic patients with positive preoperative RT-PCR results and the incidence and factors associated with postoperative SARS-CoV-2 infection in patients with cancer referred for elective surgery. Patients with elective surgery between May and October 2020 were included. RT-PCR of nasopharyngeal swabs was performed preoperatively for all patients. Postoperative SARS-CoV-2 infection was assessed within 30 postoperative days. RESULTS: A total of 1636 preoperative screening RT-PCR tests were performed. Of these, 102 (6.2%) cases were positive, and 1,298 surgical procedures were analyzed. The postoperative SARS-CoV-2 infection rate was 0.9%. The length of stay (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.04-1.11; p < 0.001), surgical time (OR 1.004; 95% CI 1.001-1.008; p = 0.023), intensive care unit admission (OR 7.7; 95% CI 2.03-29.28; p = 0.003), and hospital readmissions (OR 9.56; 95% CI 2.50-36.56; p = 0.001) were associated with postoperative coronavirus disease (COVID-19). Using unadjusted and adjusted logistic regression, length of stay (OR 1.08; 95% CI 1.04-1.11; p < 0.001), and readmission (OR 9.02; 95% CI 2.30-35.48; p = 0.002) were independent factors of postoperative COVID-19. CONCLUSIONS: Screening patients preoperatively may reduce in-hospital SARS-CoV-2 transmission. Length of stay and readmission were independently correlated with postoperative COVID-19.

PROPER-PRehabilitatiOn Plus Enhanced Recovery after surgery versus enhanced recovery after surgery in gynecologic oncology: a randomized clinical trial.

BACKGROUND: Prehabilitation is a process that occurs before surgery and aims to improve patient functional capacity and enhance surgical recovery. This process includes medical, nutritional, physical, and psychological interventions that may reduce the duration of hospital stay and provide postoperative physical benefits. PRIMARY OBJECTIVE: To evaluate the impact of a prehabilitation program on postoperative recovery time for patients who will undergo gynecological surgery following the Enhanced Recovery After Surgery (ERAS) guidelines. STUDY HYPOTHESIS: A multidisciplinary, preoperative prehabilitation program for patients who will undergo gynecological surgery leads to a reduction in the length of hospital stay and improves patient functional capacity. TRIAL DESIGN: Prospective, interventionist, and randomized controlled trial in a 1:1 ratio, open to multidisciplinary team and patients, blinded to surgeons and anesthesiologists. The control group will undergo ERAS standard preoperative care while the intervention group will have ERAS standard preoperative care plus prehabilitation. MAJOR INCLUSION CRITERIA: Patients scheduled to undergo gynecologic surgery performed by laparotomy with a preoperative schedule that allows prehabilitation intervention for 2 to 3 weeks. PRIMARY ENDPOINT: To compare time between surgery and the day the patient is ready for discharge in patients who underwent the prehabilitation process versus those who did not. Readiness for discharge is defined as the ability to take care of one's-self, to walk alone, and to ingest at least 75% of daily recommended calorie intake. SAMPLE SIZE: 194 participants ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 30 patients have been recruited. Accrual should be completed by 2023-24. TRIAL REGISTRATION: The study is approved by the IBCC - São Camilo Oncologia ethics committee (reference number 4.256.553) and is registered at clinicaltrials.gov (NCT04596800).

Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study.

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

Cardiophrenic lymph node resection in cytoreduction for primary advanced or recurrent epithelial ovarian carcinoma: a cohort study.

OBJECTIVES: To evaluate the clinical outcomes of epithelial ovarian carcinoma patients who underwent cardiophrenic lymph node resection. METHODS: We retrospectively reviewed the records of all surgically treated patients with advanced epithelial ovarian carcinoma (stages IIIC-IV) who underwent cardiophrenic lymph node resection between 2002 and 2018. Only those in whom cardiophrenic lymph node involvement was the only detectable extra-abdominal disease were included. Patients with suspected cardiophrenic lymph node metastasis on staging images underwent a transdiaphragmatic incision to access the para-cardiac space after complete abdominal cytoreduction achievement. Data on disease-free survival, overall survival, and surgical procedures performed concurrently with cardiophrenic lymph node resection were collected. RESULTS: Of the total 456 patients, 29 underwent cardiophrenic lymph node resection; of these, 24 patients met the inclusion criteria. Twenty-two, one, and one patients had high grade serous epithelial ovarian carcinoma, low grade epithelial ovarian carcinoma, and ovarian carcinosarcoma, respectively. Ten patients had recurrent disease (recurrence group). Fourteen patients underwent cytoreduction during primary treatment (primary debulking group); four underwent cytoreduction after neoadjuvant chemotherapy. Cardiophrenic lymph node resection was performed on the right side in 19 patients, left side in three, and bilaterally in two. The average procedural duration was 28 minutes, with minimal blood loss and no severe complications. Twenty-one patients had cardiophrenic lymph node positivity. The median disease-free intervals were 17 and 12 months in the recurrent and primary debulking surgery groups, respectively. The mediastinum was the first recurrence site in 10 patients. Five patients developed brain metastases. Five patients had an overall survival beyond 50 months. CONCLUSIONS: Although rare, the cardiophrenic lymph nodes may be a site of metastasis of ovarian cancer. Although their presence might indicate future recurrence, some patients may achieve long-term survival. Resection should be considered in cases of suspicious involvement to confirm extra-abdominal disease and achieve complete cytoreduction.

Prevalence of anticipatory nausea and vomiting in breast cancer patients undergoing highly emetogenic chemotherapy.

OBJECTIVE: Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist. METHODS: This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2. RESULTS: From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003). CONCLUSION: The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.

High mortality among patients with cancer and COVID-19 infection: the experience of a Brazilian cancer center.

OBJECTIVE: To evaluate the severity of COVID-19 in cancer patients to describe clinical and epidemiological factors associated with poor outcomes (mortality and need of intensive care unit admission or mechanical ventilation). METHODS: Retrospective data from patients with cancer and laboratory diagnosis of COVID-19, obtained between March 16 and May 29, 2020, were retrieved out of a cancer center database. Data analyzed included patient history, age, sex, comorbidities, types of cancer and anticancer therapy. RESULTS: This sample comprised 105 patients aged 18-92 years, 80.9% of whom were females. Dyspnea was the most prevalent initial symptom (30.4%) among patients who died (p<0.0001). Overall, 57.1% of patients had metastatic disease and 60% had poor performance status (Eastern Cooperative Oncologic Group ≥2) at the time of COVID-19 diagnosis. The overall mortality rate was 40.95%. Mortality rates were higher in male patients and those with poor performance status (p<0.0001). CONCLUSION: This cohort is one of the largest Brazilian studies describing clinical and epidemiological features of patients with cancer and concurrent COVID-19. Findings of this study emphasize the vulnerability of cancer patients in the current pandemic, and indicate high mortality from COVID-19 among male cancer patients and cancer patients with poor performance status. This analysis may assist the selection of patients who may benefit from strict isolation and eventual discontinuation of anticancer therapy to reduce exposure to infection.

Prevalence of anticipatory nausea and vomiting in breast cancer patients undergoing highly emetogenic chemotherapy

SUMMARY OBJECTIVE: Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist. METHODS: This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2. RESULTS: From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003). CONCLUSION: The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.

Estudo de fase II de pregabalina para prevenção de náuseas e vômitos induzidos por quimioterapia / Phase II study of pregabalin for the prevention of chemotherapy induced nausea and vomiting

Para avaliar o papel da pregabalina na proteção das náuseas e vômitos induzidos pela quimioterapia, foi realizado um ensaio clínico de fase II, aleatorizado, duplamente cego, controlado por placebo, para investigar se a pregabalina poderia melhorar o controle completo das náuseas e vômitos (desfecho primário). Inscrevemos 82 pacientes virgens de quimioterapia, programados para receber quimioterapia moderadamente e altamente emetogênica. Todos os doentes receberam ondansetron 8mg por via intravenosa, dexametasona 10mg antes da quimioterapia no primeiro dia e, dexametasona 4 mg por via oral, b.d., nos dias dois e três. Os doentes foram distribuídos aleatoriamente para tomar pregabalina 75 mg ou placebo, bd, desde a noite anterior à quimioterapia até ao quinto dia. A resposta completa global não foi estatisticamente significativa entre os grupos (53,7 versus 48,8%, respetivamente, no grupo da pregabalina e no grupo de controlo (P=0,65)). Também não houve diferença estatística significativa durante a fase aguda (primeiras 24 horas) e a fase tardia (24-120h): 80,5% versus 82,9% (P=0,77), 53,7 versus 51,2% (P=0,82), respectivamente. Neste estudo não foi identificada ação da pregabalina na prevenção de náuseas e vômitos induzidos por quimioterapia. Número de registo no Clinicaltrial.gov: NCT04181346.

To evaluate the role of pregabalin in the protection of chemotherapy-induced nausea and vomiting, we performed a phase II randomized, double-blind, placebo-controlled trial to investigate whether pregabalin could improve the complete control of nausea and vomiting (primary end point). We enrolled 82 chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy. All patients received IV ondansetron 8mg, dexamethasone 10mg before chemotherapy on day one and oral dexamethasone 4mg, b.d., on days two and three. Patients were randomly assigned to take pregabalin 75mg or placebo, bd, from the night before chemotherapy to day five. The overall complete response was not statistically significant between the groups (53.7 versus 48.8%, respectively, in the pregabalin group and the control group (P=0.65)). There was also no significant difference during the acute phase (first 24 hours) and delayed phase (24-120h): 80.5% versus 82.9% (P=0.77), 53.7 versus 51.2% (P=0.82), respectively. There is no role for pregabalin preventing chemotherapy-induced nausea and vomiting. Clinicaltrial.gov registration number: NCT04181346.

High mortality among patients with cancer and COVID-19 infection: the experience of a Brazilian cancer center / Alta mortalidade entre pacientes com câncer e infecção por COVID-19: a experiência de um centro oncológico brasileiro

ABSTRACT Objective To evaluate the severity of COVID-19 in cancer patients to describe clinical and epidemiological factors associated with poor outcomes (mortality and need of intensive care unit admission or mechanical ventilation). Methods Retrospective data from patients with cancer and laboratory diagnosis of COVID-19, obtained between March 16 and May 29, 2020, were retrieved out of a cancer center database. Data analyzed included patient history, age, sex, comorbidities, types of cancer and anticancer therapy. Results This sample comprised 105 patients aged 18-92 years, 80.9% of whom were females. Dyspnea was the most prevalent initial symptom (30.4%) among patients who died (p<0.0001). Overall, 57.1% of patients had metastatic disease and 60% had poor performance status (Eastern Cooperative Oncologic Group ≥2) at the time of COVID-19 diagnosis. The overall mortality rate was 40.95%. Mortality rates were higher in male patients and those with poor performance status (p<0.0001). Conclusion This cohort is one of the largest Brazilian studies describing clinical and epidemiological features of patients with cancer and concurrent COVID-19. Findings of this study emphasize the vulnerability of cancer patients in the current pandemic, and indicate high mortality from COVID-19 among male cancer patients and cancer patients with poor performance status. This analysis may assist the selection of patients who may benefit from strict isolation and eventual discontinuation of anticancer therapy to reduce exposure to infection.

RESUMO Objetivo Avaliar a gravidade da infecção por COVID-19 em pacientes oncológicos, determinando os aspectos clínicos e epidemiológicos associados ao pior desfecho, seja em termos de mortalidade, necessidade de internação em unidade de terapia intensiva ou ventilação mecânica. Métodos Pacientes com câncer e diagnóstico confirmado por laboratório de COVID-19 foram identificados nos bancos de dados de um hospital oncológico entre 16 de março e 29 de maio de 2020. Os dados coletados incluíram história, idade, sexo e comorbidades dos pacientes, além dos tipos de câncer e do tratamento anticâncer. Resultados Dentre os 105 pacientes analisados, a idade variou de 18 a 92 anos, e 80,9% eram do sexo feminino. Dispneia foi o sintoma inicial mais prevalente entre os que morreram (30,4%). No momento do diagnóstico da infecção, 57,1% apresentavam doença metastática e 60% performance status ruim (Eastern Cooperative Oncologic Group ≥2). A taxa de mortalidade geral foi 40,95% e superior entre os homens e pacientes com baixo nível de performance status (p<0,0001). Conclusão Este coorte é um dos estudos mais robustos do Brasil, descrevendo características clínicas e epidemiológicas de pacientes com câncer e COVID-19. Os achados do estudo alertam para a vulnerabilidade dos pacientes oncológicos na pandemia atual e demonstram alta mortalidade por COVID-19 em pacientes do sexo masculino e com pior performance status. Essa análise pode ajudar a selecionar os pacientes que podem se beneficiar de isolamento rigoroso e até mesmo da interrupção do tratamento, reduzindo a exposição à infecção.