Unplanned Hospital Admissions in Patients With Solid Tumors in Brazil: Causes and Progressive Disease's Impact on Outcomes.

PURPOSE: Most patients with cancer will be hospitalized throughout the disease course. However, most evidence on the causes and outcomes of these hospitalizations comes from administrative data or small retrospective studies from high-income countries. METHODS: This study is a retrospective cohort of patients with solid tumors hospitalized from February 1, 2021, to December 31, 2021, in a tertiary cancer center in São Paulo, Brazil. We collected data on cancer diagnosis, symptoms at admission, hospitalization diagnosis, and survival clinical outcomes during in-hospital stay (in-hospital mortality) and after discharge (readmission rates and overall survival [OS]). Progressive disease (PD) diagnosis during admission was retrieved from manual chart review if explicitly stated by the attending physician. We modeled in-hospital mortality and postdischarge OS with logistic regression and Cox proportional hazards models, respectively. RESULTS: A total of 3,726 unique unplanned admissions were identified. The most common symptoms at admission were pain (40.6%), nausea (16.8%), and dyspnea (16.1%). PD (34.0%), infection (31.1%), and cancer pain (13.4%) were the most frequent reasons for admission. The in-hospital mortality rate was 18.9%. Patients with PD had a high in-hospital mortality rate across all tumor groups and higher odds of in-hospital death (odds ratio, 3.5 [95% CI, 3.0 to 4.2]). The 7-, 30-, and 90-day readmission rates were 11.9%, 33.5%, and 54%, respectively. The postdischarge median OS (mOS) was 12.6 months (95% CI, 11.6 to 13.7). Poorer postdischarge survival was observed among patients with PD (mOS, 5 months v 18 months; P < .001; hazard ratio, 2.4 [95% CI, 2.1 to 2.6]). CONCLUSION: PD is a common diagnosis during unplanned hospitalizations and is associated with higher in-hospital mortality rates and poorer OS after discharge. Oncologists should be aware of the prognostic implications of PD during admission and align goals of care with their patients.

Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Frequency of Radiation Therapy-Induced Malignancies in Patients With Li-Fraumeni Syndrome and Early-Stage Breast Cancer and the Influence of Radiation Therapy Technique.

PURPOSE: Breast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a condition associated with an increased risk of various malignancies, including radiation therapy (RT)-induced malignancies (RIM) within previously irradiated areas. Our study aimed to assess the incidence of RIM in patients with LFS and early-stage BC treated with adjuvant RT, including the effect of RT dose and technique. METHODS AND MATERIALS: We examined patients with a germline pathogenic/likely pathogenic TP53 variant diagnosed with early-stage BC and monitored by a hereditary cancer team at a single cancer center. The study endpoints included RIM frequency, the association of RIM with the dose and type of RT (2-dimensional [2D] RT, 3-dimensional [3D] RT, and intensity modulated RT [IMRT]), and BC recurrence. RESULTS: We analyzed 48 patients with a median age of 39 years (range, 21-62). The majority (71%) had the TP53 R337H variant, and 87% were unaware of their LFS diagnosis at the time of BC treatment. Treatment modalities included mastectomy (62%), (neo)adjuvant chemotherapy (66%), and RT (62%), with RT being more common after breast-conserving surgery (87% vs 46% with mastectomy, P = .010). Among the 30 patients treated with RT, 10% developed RIM in the irradiated field, consisting of 3 soft tissue malignancies. RT dose (≤40.8 or >40.8 Gy) did not influence RIM occurrence, but the type of RT did. RIM was observed in 100% of cases with 2D RT (2/2), 50% with IMRT (1/2), and 0% with 3D RT (0/16) (P = .004). CONCLUSIONS: Our study underscores a concerning rate of RIM after adjuvant RT, emphasizing the importance of a thorough risk-benefit evaluation before recommending RT, with preference for its avoidance if possible. Although subgroup sizes were limited, the risk of RIM appeared to be influenced by the RT technique, with higher rates observed with 2D RT and IMRT compared with 3D RT. Early TP53 testing is essential to guide the BC treatment plan.

Oncology and Palliative Care Integration Model: A Cost Analysis Study in a Brazilian Hospital Setting.

Background: In 2019, the São Paulo State Cancer Institute (ICESP) implemented a novel model integrating Oncology with Palliative Care specialists. We evaluated the impact of this model on healthcare resource utilization and costs. Methods: We analyzed data from all patients who passed away in February (1 month prior to implementation) and November (8 months after model implementation group) at ICESP, Brazil. Healthcare utilization data, including emergency department visits, hospital and intensive care unit admissions, chemotherapy, and radiotherapy use, were retrieved from Electronic Medical Records. Unit cost values were obtained from the administrative database. Results: A total of 198 patients who died in February and 196 in November were included in the analysis. Groups exhibited similarities in sex, age, ECOG, cancer type, previous outpatient palliative care consultations, and place of death (ward: 56.6% pre-intervention, 50% post-intervention). The mean cost per patient was US$13,226.29 pre-intervention and US$11,445.82 post-intervention (P = .007). Statistically significant differences were noted in days hospitalized in the surgical ward (227 vs 115), emergency department visits (233 vs 45), chemotherapy sessions (140 vs 26), and radiotherapy sessions (146 vs 10). Excluding outpatient treatments, the total costs for chemotherapy and radiotherapy in the last 30 days of life were US$16,924.45 pre-intervention and US$7851.65 post-intervention. Reductions were more pronounced in patients with ECOG 3-4 (P = .039). Conclusion: Our data suggests that the integration model was associated with a reduction in potentially inappropriate treatments during the last month of life, leading to decreased healthcare utilization and costs.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial.

BACKGROUND: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer. METHODS: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m2) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866. FINDINGS: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy). INTERPRETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care. FUNDING: AstraZeneca.

A matched case-control study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome (BREAST TP53).

INTRODUCTION: Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS. METHODS: We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS). RESULTS: Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95%CI 0.74-8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25-13.48, P = 0.534). CONCLUSIONS: Our results showed no statistically significant difference in BC-related RFS and BCSS between patients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results.

Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of College of American Pathologists Guideline.

PURPOSE: The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS: The CAP guideline was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the CAP guideline, published on August 3, 2022, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer. RECOMMENDATIONS: Within the guideline, MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are all recommended testing options for colorectal cancer, MMR-IHC and MSI-polymerase chain reaction for gastroesophageal and small bowel cancer, and only MMR-IHC for endometrial cancer. No recommendation in favor of any testing method over another could be made for any other cancer. Tumor mutational burden was not recommended as a surrogate for DNA MMR deficiency. If MMR deficiency consistent with Lynch syndrome is detected, it should be communicated to the treating physician.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.

Multiple Criteria Decision Analysis (MCDA) for evaluating cancer treatments in hospital-based health technology assessment: The Paraconsistent Value Framework.

BACKGROUND: In recent years, the potential of multi-criteria decision analysis (MCDA) in the health field has been discussed widely. However, most MCDA methodologies have given little attention to the aggregation of different stakeholder individual perspectives. OBJECTIVE: To illustrate how a paraconsistent theory-based MCDA reusable framework, designed to aid hospital-based Health Technology Assessment (HTA), could be used to aggregate individual expert perspectives when valuing cancer treatments. METHODS: An MCDA methodological process was adopted based on paraconsistent theory and following ISPOR recommended steps in conducting an MCDA study. A proof-of-concept exercise focusing on identifying and assessing the global value of first-line treatments for metastatic colorectal cancer (mCRC) was conducted to foster the development of the MCDA framework. RESULTS: On consultation with hospital-based HTA committee members, 11 perspectives were considered in an expert panel: medical oncology, oncologic surgery, radiotherapy, palliative care, pharmacist, health economist, epidemiologist, public health expert, health media expert, pharmaceutical industry, and patient advocate. The highest weights were assigned to the criteria "overall survival" (mean 0.22), "burden of disease" (mean 0.21) and "adverse events" (mean 0.20), and the lowest weights were given to "progression-free survival" and "cost of treatment" (mean 0.18 for both). FOLFIRI and mFlox scored the highest global value score of 0.75, followed by mFOLFOX6 with a global value score of 0.71. mIFL was ranked last with a global value score of 0.62. The paraconsistent analysis (para-analysis) of 6 first-line treatments for mCRC indicated that FOLFIRI and mFlox were the appropriate options for reimbursement in the context of this study. CONCLUSION: The Paraconsistent Value Framework is proposed as a step beyond the current MCDA practices, in order to improve means of dealing with individual expert perspectives in hospital-based HTA of cancer treatments.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors.

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil.

BACKGROUND: Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancers has brought considerable benefits to disease-free survival and overall survival. OBJECTIVE: To conduct a cost-effectiveness analysis of the treatment of patients with early and locally advanced HER2 positive breast cancer, within the scope of the Brazilian public health system, comparing adjuvant chemotherapy with and without trastuzumab, for 1 year of treatment. METHODS: A 4-state Markov model was developed to estimate strategy costs and outcomes. RESULTS: Based on the proposed model, we verified an incremental benefit of trastuzumab therapy compared to treatment without trastuzumab with 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG). The use of adjuvant chemotherapy with trastuzumab has an ICER of US$19,599.26 for each quality-adjusted life year and US$14,180.68 for each life year gained in relation to chemotherapy without trastuzumab. CONCLUSION: In Brazil, adjuvant chemotherapy with trastuzumab may be considered cost-effective only if a cost-effectiveness threshold is stipulated with the value starting at three times the Brazilian GDP per capita for QALY or two times the Brazilian GDP per capita for LYG, from health system perspective.

Impact of the COVID-19 pandemic on breast and cervical cancer stage at diagnosis in Brazil.

BACKGROUND: The COVID-19 pandemic has led to the need for health services adjustments, which may have compromised management of other diseases. For cancer patients, delays may significantly impair outcomes in some situations. We aimed to assess the impact of the COVID-19 pandemic in breast and cervical cancer diagnosis and treatment compared to the same period prior to the pandemic. METHODS: Data were collected from patients attending their first visit to a Brazilian cancer centre from 1 September 2020 to 31 January 2021 and from 1 September 2019 to 31 January 2020. The pandemic started in February 2020 in Brazil and is still ongoing. We considered this period (September/20-January/21) to be representative of the pandemic impact on cancer management. The primary endpoint was breast and cervical cancer stages at diagnosis. RESULTS: A total of 268 breast cancer patients and 44 cervical cancer patients had their first consult in our cancer centre from September/20 to January/21; 457 and 60, respectively, occurred from September/19 to January/20. Patients who attended their first visit during the pandemic (September/20-January/21) presented with more advanced-stage breast cancer (p < 0.001) and cervical cancer (p = 0.328) than those in the period prior to the pandemic (September/19-January/20), although the difference was not statistically significant for cervical cancer. The proportion of cervical cancer patients diagnosed with locally advanced disease (stages III-IVA) was 56.8% (N = 25) in September/20-January/21 compared to 43.3% (N = 26) in September/19-January/20. Similarly, 37.3% (N = 100) of breast cancer patients had stage III disease in September/20-January/21 compared to 23.2% (N = 106) in September/19-January/20. Fewer breast cancer patients (13.7%) were diagnosed due to screening tests during the pandemic than before it (25.5%) (p < 0.001). CONCLUSIONS: Breast and cervical cancer patients had more advanced-stage diseases in their first visit to a cancer centre during the COVID-19 pandemic compared to a similar period prior to the pandemic. Efforts should be made not to compromise essential cancer services since this results in long-term negative impacts for oncologic patients.

Everolimus plus anastrozole for female adnexal tumor of probable Wolffian origin (FATWO) with STK11 mutation.

Female adnexal tumor of probable Wolffian origin (FATWO) are a rare type of cancer that originates from Wolffian duct remnants. Due to its rarity, no standard systemic treatment is established for cases of recurrent or metastatic disease. Previous literature reported the use of platinum-based chemotherapy and c-Kit tyrosine kinase inhibitors for FATWO cases with c-Kit positive expression. Currently, however, the broader availability of next-generation sequencing (NGS) tests allows a better molecular characterization of rare cancer such as FATWO and a possibility for the use of personalized, targeted therapy. Previous case series that performed NGS for FATWO patients described the presence of STK11 mutations in a considerable number of cases, representing a potential target in this population. To our knowledge, we describe here the first case report of a patient with FATWO and STK11 mutation exhibiting a considerable and durable response after treatment with an mTOR inhibitor plus endocrine therapy.

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer.

OBJECTIVE: This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer. METHODS: Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee. RESULTS: At data cutoff, 161 women (median age, 53 years [range 25-81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%-21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%-57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events. CONCLUSION: Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer.

Outcomes and Prognostic Factors in a Large Cohort of Hospitalized Cancer Patients With COVID-19.

PURPOSE: Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS: All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS: Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION: A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

Challenge of Incorporating New Drugs for Breast Cancer in Brazil: A Proposed Framework for Improving Access to Innovative Therapies.

PURPOSE: The objective of this review is to address the barriers limiting access to treatment of advanced metastatic breast cancer (mBC) in Brazil, specifically for patients in the public health care system, arguably those with the least access to innovation. MATERIALS AND METHODS: A selected panel of Brazilian experts in BC were provided with a series of relevant questions to address in a multiday conference. During the conference, responses were discussed and edited by the entire group through numerous drafts and rounds of discussion until a consensus was achieved. RESULTS: The authors propose specific and realistic recommendations for implementing access to new drugs in cancer care in Brazil. Moreover, in creating these recommendations and framework, the authors strive to address the most important barriers and impediments for technology incorporation. A feasible and specific multidisciplinary process is proposed, which is based on the collective participation of all involved stakeholders. CONCLUSION: Given the current benefits and likely future developments, there is a great need to expand treatments for mBC not only in Brazil but also in most other countries in the world where access issues remain an unresolved demand. Adapting the current framework is essential for accomplishing this goal. The recommendations in this review can serve as a framework for adoption of new technologies in countries with limited resources.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission.

OBJECTIVE: To investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy. METHODS: This single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics. RESULTS: Twenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6-13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%). CONCLUSIONS: Hu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy. TRIAL REGISTRATION: NCT01137071.

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.