Cancer Study Group Research Articles

Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer

BackgroundAdjuvant aromatase inhibitors increase osteoporosis and fractures in patients with hormone receptor–positive breast cancer. We have previously reported outcomes of the ABCSG-18 (study 18 from the Austrian Breast & Colorectal Cancer Study Group) trial showing that adjuvant anti–receptor activator of nuclear factor-κB ligand denosumab treatment counteracts these adverse effects and may improve outcomes. We report here the final long-term outcomes.MethodsABCSG-18 is a prospective, double-blind, placebo-controlled, phase 3 trial in which 3425 postmenopausal patients with early hormone receptor–positive breast cancer receiving aromatase inhibitor therapy were randomly assigned in 58 trial centers to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months. The primary end point was the time to first clinical fracture after randomization. Secondary disease outcome–related end points were disease-free survival (DFS), bone metastasis–free survival (BMFS), and overall survival (OS).ResultsFor this final protocol-defined analysis, median follow-up is 8 years (interquartile range, 6 to 9.6 years). There were 309 versus 368 DFS events (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.97) in the denosumab versus the placebo group, respectively, resulting in an absolute 9-year DFS benefit of 3.5 percentage points (79.4 vs. 75.9%). Adjuvant denosumab improved BMFS by 2.5 percentage points (88.9 vs. 86.4%; hazard ratio, 0.81; 95% CI, 0.65 to 1.00) and OS by 1.0 percentage point (90.9 vs. 89.9%; hazard ratio, 0.80; 95% CI, 0.64 to 1.01). No new toxicities for this dose of adjuvant denosumab were observed.ConclusionsDFS, BMFS, and OS continued to show benefit in this final long-term analysis of ABCSG-18. There were no new toxicities. (Funded by Amgen; ClinicalTrials.gov number, NCT00556374.)

A Multicenter Prospective Study for Validation of the Korean Simple Geriatric Assessment Tool in Elderly Patients with Multiple Myeloma

Purpose Frailty is a multidimensional state of diminished reserve (energy, physical ability, cognition and health) which gives rise to vulnerability to cancer treatment. Geriatric assessment (GA) with management should be integrated into the clinical care of older patients with multiple myeloma (MM). with ageing-related conditions. The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a simplified frailty assessment tool, in older patients with multiple myeloma (MM) planned to undergo first-line chemotherapy. Materials and Methods The study included 95 newly diagnosed MM patients aged 70 years or older. Participants answered the KG-7 questionnaire before undergoing International Myeloma Working Group (IMWG) frailty score and first-line bortezomib- and/or lenalidomide- based chemotherapy. KG-7 scores ranged from 0 to 7, and higher scores indicated better conditions. Results The median age was 77 years and 50.5% of patients were older than 75 years. Fifteen patients (15.8%) had an ADL score ≤ 4, 24 (25.3%) an IADL score ≤ 5, and 19 (20.0%) a CCI ≥ 2. Based on the < 5 cut-off value of KG-7 for frail group, frail group was shown in 29 (30.5%). There was the negative correlation between KG-7 and IMWG frailty score (Pearson correlation, 0.547; P < 0.001). The cumulative incidence of grade ≥ 3 non-hematologic adverse events was 27.3% in non-frail and 48.3% in frail patients (HR, 2.5; P = 0.046). There was no significant difference between the two groups of KG-7 with regard to grade ≥ 3 hematological toxicity and dose modification at cycle one. There was no significant difference between the two groups (frail versus non-frail) in PFS (hazard ratio [HR] = 1.37; 95% CI = 0.52-3.65; P = 0.525) and OS (HR = 1.85; 95% CI 0.52-6.58, P = 0.341), which was attributed to the short FU period of 11.6 months. Interpretation Despite the interim analysis, KG-7 appears to be an easy-to-define prediction model for defining the vulnerable patients with MM. Whether KG-7 is helpful in predicting survival outcome requires longer follow-up.

Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies.

The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.

Radiation Therapy for Low-Risk Breast Cancer: Whole, Partial, or None?

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.The following case represents a relatively common clinical scenario of a postmenopausal female patient who presents with low-risk, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative, early-stage, left-sided breast cancer to discuss the role of postoperative radiation (RT) following wide local excision (WLE) and sentinel node biopsy. The spectrum of choices, ranging from omission of RT, accelerated partial breast irradiation (PBI), whole-breast radiation therapy, and the nuances of various dose/fractionation regimens for each option, are discussed in the context of the Danish Breast Cancer Study Group (DBCSG) PBI trial published in this issue, with additional review of other key trials that inform these treatment recommendations. After consideration of the clinical-pathologic features in the framework of the existing data and an in-depth discussion taking into consideration the patient's preferences/goals, the decision was made to deliver moderately hypofractionated RT (40 Gy/15 fractions) to a PBI volume, in concordance with the DBCSG-PBI trial.

Sex differences in clinico-pathologic characteristics and long-term survival among 17,192 surgically treated NSCLC patients: Nationwide population-based propensity score-matching study

IntroductionMore information is needed on gender differences in lung cancer surgery. Thus, we conducted a retrospective study on thoracic treatment of non-small cell lung cancer (NSCLC) patients between 2007 and 2020 in Poland. The aim was to characterize sex differences in survival after complete surgical resection and to compare postoperative complications between Polish men and women. The main aspects that were compared between women and men were as follows: type of surgery and postoperative staging, morbidity and mortality, thoracic surgery complications, comorbidities, and overall survival based on a univariate analysis including propensity score matching (PSM) and a multivariate analysis. Materials and MethodsData were collected retrospectively from the Polish Lung Cancer Study Group database. Patients who were surgically treated for NSCLC between 2007 and 2020 (n = 17,192) were included in the study. ResultsThe univariate analysis showed significantly better survival in women than in men. Women had better 5-year survival compared to men both for adenocarcinoma and squamous cell carcinoma (66% vs. 53%, p < 0.0001 and 65% vs. 51%, p<0.0001%, respectively), for both smokers and non-smokers (65% vs. 52%, p < 0.0001 and 65% vs. 51%, p < 0.0001, respectively), all age groups, and all stages (IA1 to III B). In the PSM analysis, statistically significant differences in favor of women were found for lower lobectomy (67% vs. 50%, p < 0.0001) and upper lobectomy (67% vs. 56%, p < 0.0001). Overall, postoperative complications occurred in 33.1% of patients and were observed more often in men than in women (35.8% vs. 28.6%, p < 0.001). ConclusionsWomen with NSCLC who were treated surgically had a better long-term outcome compared to men, with no significant difference in disease severity. In addition to gender, the histological type, comorbidities, and type of surgery and surgical approach are also important.

Pushing the Limits: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Advanced Hepatocellular Carcinoma with Macrovascular Invasion

INTRODUCTION: Patients with advanced hepatocellular carcinoma and macrovascular invasion (MVI) have dismal prognosis and are referred to systemic treatment or palliation. The aim of this study is the investigation the outcomes of patients with HCC and MVI undergoing operation in the form of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. METHODS: Demographics and operative data as well as follow-up were retrospectively reviewed. All types of hepatectomy and all types of ALPPS modification were included. MVI was categorized according to the Japanese Liver Cancer Study Group classification. RESULTS: A total of 28 patients were included in the study. Viral etiology was the most common cause of chronic liver disease (89.3%); 85.7% of patients were cirrhotic, with a median Model for End-Stage Liver Disease score of 9 (7 to 10). MVI of the hepatic veins or inferior vena cava was diagnosed in 46.4% of patients, and portal vein involvement was present in 64.2% of cases. Four patients (14.2%) were diagnosed with bile duct involvement. No patients died after step 1, although complication occurred in 21.4% of cases. After step 2, 3 patients (11.5%) died and 20 (69.2%) developed complication. Grade B and C after hepatectomy liver failure occurred in 57.6% and 11.5% of patients, respectively. After a median follow-up of 18 months (7 to 35), median survival was 22 months (3 to 40). Eleven patients (39.3%) experienced recurrence. Median disease-free survival was 15 months (5 to 26). CONCLUSION: The ALPPS procedure is an extreme rescue approach in otherwise inoperable advanced HCC with MVI. The procedure is associated with high morbidity and mortality and patient selection is pivotal. Oncologic outcomes are safe and should be further investigated.

Report of Chinese Children's Cancer Group acute lymphoblastic leukemia 2015 multicenter study

Objective: To evaluate the outcomes and identify the prognostic factors of childhood acute lymphoblastic leukemia (ALL) treated with Chinese Children's Cancer Group study ALL-2015 (CCCG-ALL-2015) protocol. Methods: There were two randomization studies in CCCG-ALL-2015 study. A total of 7 640 newly diagnosed ALL patients in 20 hospitals of multi-institutional study group between January 2015 and December 2019 were treated with unified protocol. CCCG-ALL-2015 protocol featured risk-directed therapy based on morphology, immunophenotype, and genetic features, and adjusted according to minimal residual disease (MRD) assay on day 19 and day 46 of induction, which totally omitted prophylactic cranial irradiation. Two randomized controlled trails were designed. Children with Philadelphia chromosome-positive ALL (Ph+ALL) were randomly treated with dasatinib (Ph-D group) or imatinib (Ph-I group). During the latter half of continuation therapy, children were randomly treated with seven pulses of vincristine plus dexamethasone (group A) or not (group B). The survival rates of different groups were compared. Event-free survival (EFS) and overall survival (OS) curves were estimated according to the Kaplan-Meier method and compared by Log-rank test. Cox proportional hazards model was used for multivariate analysis. Results: Of the 7 640 enrolled patients, there were 4 521 males and 3 119 females, 7 508 (98.3%) entered complete remission. The 5-year EFS was 60.1% (95%CI 49.8%-72.5%) in the Ph-D group and 39.4% (95%CI 26.9%-57.7%) in the Ph-I group (χ2=5.00, P=0.020). Between patients with lower risk (LR) and intermediate and higher risk (I/HR) treated with (group A) or without (group B) additional pulse of vincristine plus dexamethasone, there were no difference in 5-year EFS and OS. The one-sided 95% upper confidence bound for the difference in 5-year EFS and OS were 0.02 and 0.01 for LR, 0.05 and 0.01 for I/HR, establishing non-inferiority, lower than 0.05. The follow-up time was 3.5 (2.4,4.8) years. The 5-year OS was 90.9% (95%CI 90.2%-91.7%), and EFS was 80.1% (95%CI 79.0%-81.2%). The 5-year cumulative risk of any relapse was 15.3% (95%CI 14.3%-16.3%).The cumulative risk of isolated central nervous system (CNS) relapse was 1.9% (95%CI 1.6%-2.2%), and any CNS relapse 2.7% (95%CI 2.3%-3.1%). The 5-year cumulative risk of death during remission was 1.3% (95%CI 1.0%-1.6%). In the multivariate analysis, the independent factors associated with inferior EFS of patients with B-ALL were age≥10 years, male sex, white blood cell count ≥50×109/L, CNS2 or CNS3 status, BCR-ABL fusion, KMT2A rearrangements, without ETV6-RUNX1 fusion and the presence of MRD>0.01% at day 19 or 46 (all P<0.05). Among patients with T-ALL, the significant predictors for lower EFS were the BCR-ABL1 fusion and MRD≥0.10% at day 46 (both P<0.05). Conclusions: Patients treated with CCCG-ALL-2015 protocol without the use of prophylactic cranial irradiation have favorable outcomes, and the cumulative risk of isolated CNS relapse and cumulative risk of death during remission are low. Intensive chemotherapy including dasatinib yield superior results compared to imatinib in the treatment of Ph+ALL. Vincristine plus dexamethasone pulses can be omitted for ALL children without decrease in treatment ontcome during the latter half of continuation therapy.

European multicenter propensity score match study of laparoscopic vs. open colectomy for splenic flexure carcinomas: Results from the Splenic Flexure Cancer (SFC) Study Group.

This European multicenter study aims to compare the results of laparoscopic versus laparotomy approach for the resection of splenic flexure colon carcinoma (SFC). Patients with SFC who required curative resection by laparoscopy (LAP) or laparotomy (OPEN) between 2000 and 2018 were included. Three types of interventions were considered: extended right hemi-colectomy, left hemi-colectomy and splenic flexure resection. The LAP and OPEN groups were matched according to propensity score and compared with Chi-square, Mann-Whitney tests, and multivariate regression models. Overall survival and recurrence-free survival were assessed using the Kaplan-Meier method. The study population consisted of 399 patients, including 297 operated by LAP and 102 by OPEN. Extended right hemi-colectomy was performed in 35.8% of cases, left hemi-colectomy in 32.8% and splenic flexure resection in 31.4%. After propensity score matching, the LAP (n=64) and OPEN (n=64) groups were comparable for all pre-operative variables and tumor characteristics. The LAP group showed less blood loss and a shorter interval to return of transit and feeding compared to the OPEN group, regardless of the resection technique. There were no differences between the groups in terms of overall survival and 5-year recurrence-free survival. These results support the application of laparoscopy for the resection of SFC.

237 (PB117) - A phase II study to evaluate the efficacy of regorafenib in C-KIT mutated metastatic malignant melanoma patients who have progressed on first-line treatment: A Multicenter Trial of Korean Cancer Study Group (UN-14–13)

Background: C-KIT mutation is a therapeutic target for malignant melanoma, and C-KIT inhibitors such as imatinib have previously shown clinical efficacy. Regorafenib is a 3rd generation inhibitor of C-KIT and demonstrates high response rate in C-KIT mutated gastrointestinal stromal tumor. We evaluated the anti-tumor activity and safety of regorafenib in C-KIT mutated metastatic malignant melanoma patients who have progressed on first-line treatment.

Nomogram-Based Prognostic Evaluation of Gastric Cancer Patients with Low Counts of Examined Lymph Nodes Outperforms the Predictive Ability of the 7th and 8th Editions of the American Joint Committee on Cancer Staging System

BackgroundThe American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. MethodsA total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). ResultsThe 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. ConclusionsA clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.

EP04.01-011 Diagnostic Approach and Treatment of Lung Cancer Patients in Portugal: Portuguese Lung Cancer Study Group Survey

In Portugal, in 2020, 5415 new lung cancer patients were diagnosed and 4797 deaths were caused by lung cancer. Lung cancer ranks third in terms of cancer incidence and is the leading cause of cancer mortality. Early diagnosis, complete and fast patient assessment and staging, multidisciplinary approach, access to personalized medicine, new treatment options and research are essential to improve survival and quality of life. Access to clinical trials is critical for this improvement.The aim of this study is to assess the techniques available to the diagnostic work-up, treatments, the waiting time and the needs perceived by physicians.

2021 Consensus Statements on the Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma From the Korean Renal Cancer Study Group (KRoCS)

Purpose: The Korean Renal Cancer Study Group (KRoCS) provides consensus recommendations on the role of cytoreductive nephrectomy (CRN) in patients with metastatic renal cell carcinoma (mRCC).Materials and Methods: A group of mRCC experts from the Korean Urological Oncology Society convened at the 2021 KRoCS meeting on CRN for mRCC.Results: The consensus document was developed to address 4 questions related that were judged to be the most relevant to patient care: (1) Is there a role for CRN in patients planning targeted therapy? (2) Is there a role for CRN in patients planning immuno-oncology agents? (3) When is the optimal time of CRN in patients planning systemic treatment? (4) What is the ideal patient selection for CRN? The panelists have come up with following consensus. For mRCC patients, CRN should be considered only in those with IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) favorable and intermediate risk disease, regardless of the systemic treatment plans. Timing of CRN should consider the risk group as well as the number of risk factors, but is generally recommended for after assessing the degree of response to initial systemic treatment. Patients with good performance status, limited metastatic burden on top of resectable primary tumor are candidates recommended for CRN with or without metastasectomy with priority.Conclusions: In conclusion, there is still a role for CRN in the multimodality treatment of mRCC. Careful patient selection is of paramount importance. As the treatment landscape of mRCC continues to change, the role of CRN in the current immuno-oncology era will require more exploration.

Prominence of NUDT15 genetic variation associated with 6-mercaptopurine tolerance in a genome-wide association study of Japanese children with acute lymphoblastic leukaemia.

Inherited genetic variation is associated with 6-mercaptopurine (6-MP) dose reduction and frequent toxicities induced by 6-MP. However, the tolerable dose for 6-MP is not fully predicted by the known variation in NUDT15 and TPMT among Asian children with acute lymphoblastic leukaemia (ALL). We performed a genome-wide association study (GWAS) related to 6-MP dose among Japanese children with ALL. This GWAS comprised 224 patients previously enrolled in Tokyo Children's Cancer Study Group clinical studies with replication attempted in 55 patients. Genome-wide single nucleotide polymorphism (SNP) genotypes were evaluated for association with average 6-MP dose during the initial 168 days of maintenance therapy. Possible associations were observed across five gene-coding regions, among which only variants at 13q14.2 were significant and replicated genome-wide (rs116855232, NUDT15, β=-10.99, p=3.7 × 10-13 ). Notable findings were observed for variants in AFF3 (rs75364948, p=2.05 × 10-6 ) and CHST11 (rs1148407, p=2.09 × 10-6 ), but were not replicated possibly due to small numbers. A previously reported candidate SNP in MTHFR was associated with higher average 6-MP dose (rs1801133, p=0.045), and FOLH1 (rs12574928) was associated in an evaluation of candidate regions (padjust =0.013). This study provides strong evidence that rs116855232 in NUDT15 is the genetic factor predominantly associated with 6-MP tolerable dose in children in Japan.

Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study.

This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC). We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition. Patients with ICC with high budding showed significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2-2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05). High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.

Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer

Addition of immune checkpoint inhibitors to anti-ERBB2 treatment has shown synergistic efficacy in preclinical studies and is thus worth investigating as a neoadjuvant treatment to maximize efficacy and to minimize toxic effects. To determine if neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab therapy for ERBB2-positive early breast cancer warrants continuation to the next phase. This nonrandomized, open label, multicenter, phase 2 trial was conducted by the Korean Cancer Study Group and enrolled patients across 6 institutions in Korea from May 2019 to May 2020. Eligible patients were diagnosed with ERBB2-positive breast cancer (primary tumor size >2 cm or pathologically confirmed lymph node-positive cancer, without distant metastases) with a clinical stage of II or III. Patients received 6 cycles of neoadjuvant pertuzumab (840 mg at first cycle, 420 mg during subsequent cycles), atezolizumab (1200 mg), docetaxel (75 mg/m2), and trastuzumab (600 mg via subcutaneous injection) every 3 weeks, followed by surgery. Patients with pathologic complete response (pCR) received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab every 3 weeks after surgery. Patients without pCR were treated with 14 cycles of atezolizumab, 1200 mg, plus trastuzumab emtansine, 3.6 mg/kg, every 3 weeks. The primary end point was pCR rate, which was defined as the absence of invasive cancer cells in the primary tumor and regional lymph nodes (ypT0/isN0). Secondary end points included clinical objective response rate, 3-year event-free survival rate according to pCR achievement, disease-free survival, overall survival, toxic effects, and quality-of-life outcomes. A total of 67 women (median [range] age, 52 [33-74] years) were enrolled. Hormone receptor expression was positive in 32 (48%) patients. Curative surgery was performed in 65 patients because 2 patients showed disease progression during neoadjuvant treatment and their tumors became unresectable. The overall pCR rate was 61% (41 of 67 patients). The pCR rate was higher in hormone receptor-negative disease vs hormone receptor-positive disease (27 of 35 [77%] patients vs 14 of 32 [44%] patients) and in programmed cell death 1-positive expression vs programmed cell death 1-negative expression (13 of 13 [100%] patients vs 28 of 53 [53%] patients). Grade 3 and 4 neutropenia and febrile neutropenia occurred in 8 (12%) patients and 5 (8%) patients, respectively. Grade 3 and 4 immune-related adverse events occurred in only 4 patients (grade 3 skin rash, encephalitis, hepatitis, and fever). No treatment-related death occurred during the neoadjuvant phase. In this nonrandomized clinical trial, treatment with the neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab regimen in patients with stage II or III ERBB2-positive breast cancer appears to have had an acceptable pCR rate and modest toxic effects. Further investigation of this immunotherapy combination in ERBB2-positive early breast cancer is warranted. ClinicalTrials.gov Identifier: NCT03881878.

Current status of primary liver cancer and decompensated cirrhosis in Japan: launch of a nationwide registry for advanced liver diseases (REAL).

We developed a nationwide database that stores data of patients with primary liver cancer (PLC) and decompensated cirrhosis (DC) on an admission basis. A database was constructed using the National Clinical Database, a nationwide registry platform for various diseases in Japan. Mutual data exchange was possible with the Nationwide Follow-up Survey of Primary Liver Cancer in Japan by the Liver Cancer Study Group of Japan. The stored data on the admission of patients with PLC, DC, or both, included treatment details as well as patient characteristics. A total of 37,705 admissions (29,489 PLC, 10,077 DC, and 1862 for both) in 21,376 patients from 224 hospitals were analyzed. The proportions of patients with hepatitis B, hepatitis C, and non-viral etiology were 11.9%, 36.2%, and 42.6%, respectively, in PLC, and 7.5%, 23.8%, and55.0%, respectively, in DC. The mean ages (± standard deviation) on admission with PLC and DC were 73 ± 10 and 68 ± 13years, respectively. The Barcelona Clinic Liver Cancer (BCLC) stage for PLC was 0, A, B, C, and D in 22.0%, 17.1%, 29.6%, 15.1%, and 5.1%, respectively. Treatment modalities for PLC were resection, ablation, transarterial chemoembolization, and systemic therapy in 18.4%, 22.8%, 33.7%, and 11.4%, respectively. A vasopressin receptor V2 antagonist was used in 38.2% in addition to conventionally used loop diuretics and aldosterone antagonists for DC. The distribution of treatment options for PLC on admission differed from that of the initial treatment. Newly introduced drugs are widely used in patients with DC.

Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive non-small cell lung cancer in South Korea (TOAST): Korean Cancer Study Group (KCSG) LU-19-22.

BackgroundIrrespective of the first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor chosen, acquired resistance to therapy is inevitable. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options following disease progression. We assessed clinical outcomes in patients who received first-line afatinib treatment with various second-line treatments including osimertinib for patients acquiring the T790M mutation.MethodsA total of 737 EGFR mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients receiving first-line afatinib treatment were categorized by second-line treatment: T790M+ sequentially treated with osimertinib (cohort A, n=116); T790M− given chemotherapy or others (cohort B, n=143); patients with unknown T790M status (cohort C, n=111); and patients who were undergoing afatinib treatment at the time of data collection, were dead, had discontinued afatinib treatment due to serious adverse events or were lost to follow-up (cohort D, n=367). The primary outcomes were total time on treatment (TOT) and TOT for first-line (TOT-1) and second-line treatments (TOT-2). Secondary outcomes were objective response rates (ORR), overall survival (OS), and central nervous system (CNS) efficacy.ResultsMedian total TOT in cohorts A, B, C, and D were 35.10 months [95% confidence interval (CI): 30.09–43.53 months], 18.80 months (95% CI: 16.92–20.20 months), 12.00 months (95% CI: 10.22–14.98 months), and 42.60 months (95% CI: 30.95–59.23 months), respectively. The ORR of patients given afatinib was 75.7%. In patients with initial brain metastasis without local treatment, the CNS response rate was 67.0% and CNS progression-free survival was 24.70 months (95% CI: 19.84–33.15 months).ConclusionsThis study showed that sequential approach of afatinib followed by second line treatment is an effective therapeutic strategy for EGFR M+ NSCLC patients.

Innovative Strategies for Developing Biomarker-Informed Cancer Clinical Trials to Accelerate Progress in Precision Oncology in Sub-Saharan Africa.

Well-designed, pragmatic, patient-centered clinical trials in low- and middle-income countries are essential to drive approval of more effective and less toxic cancer medicines to address the rising burden of cancer among populations in low- and middle-income countries. Moreover, through reverse innovation, clinical trials informed by genomic research enable development of precision medicine strategies for underserved populations within all populations. The African continent is home to many low- and middle-income countries; yet, it has seen very few cancer clinical trials. Considering that Africa is the cradle of humanity, with its diverse populations and geography, this represents a missed opportunity to understand the heterogeneity of cancer genomes and their implications for developmental therapeutics. Since 1998, the Nigerian Breast Cancer Study Group has striven to gain a better understanding of the root causes of breast cancer and accelerate progress in clinical research that will benefit the African ancestry diaspora globally through deployment of innovative "leapfrog" technologies. The University of Chicago supports interdisciplinary and interprofessional teams of researchers through the African Cancer Leaders Institute and in partnership with the African Organization for Research and Training in Cancer. By fostering public-private partnerships, the African Organization for Research and Training in Cancer can identify and integrate significant resources needed to build regional networks and establish clinical trial coordinating centers across African countries, enabling resources to be developed and shared equitably. Such resources include a standardized curriculum for specialist training in oncology, including medical oncology and oncology nursing, to increase the numbers of qualified team leaders and principal investigators. Adequate support for study participants-financial and psychosocial-and patient navigation services will be important in growing a clinical trials network. Finally, full participation of African clinical researchers in global oncology trials will ensure workforce retention in Africa and improve financial security and job satisfaction of health professionals on the African continent.

A Machine Learning Approach to Predict the Probability of Brain Metastasis in Renal Cell Carcinoma Patients

Patients with brain metastasis (BM) have a better prognosis when it is detected early. However, current guidelines recommend brain imaging only when there are central nervous system symptoms or abnormal experimental values. Therefore, metastases are discovered later in asymptomatic patients. As a result, there is a need for an algorithm that predicts the possibility of BM using clinical data and machine learning (ML). Data from 3153 patients with renal cell carcinoma (RCC) were collected from the 11-institution Korean Renal Cancer Study group (KRoCS) database. To predict BM, clinical information of 1282 patients was extracted from the database and used to compare the performance of six ML algorithms. The final model selection was based on the area under the receiver operating characteristic (AUROC) curve. After optimizing the hyperparameters for each model, the adaptive boosting (AdaBoost) model outperformed the others, with an AUROC of 0.716. We developed an algorithm to predict the probability of BM in patients with RCC. Using the developed predictive model, it is possible to avoid detection delays by performing computed tomography scans on potentially asymptomatic patients.

Clinical Manifestations of Pulmonary Mucormycosis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A 21-Case Series Report and Literature Review.

Introduction Mucormycosis is a rare, invasive disease caused by opportunistic pathogens related to the Mucorales order with high fatality rates in immunocompromised hosts, especially in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis and treatment of pulmonary mucormycosis in recipients of allo-HSCT remains challenging. Purpose The aim of this study is to summarize and analyze the clinical features of pulmonary mucormycosis in recipients of allo-HSCT to explore further clinical research directions for this rare fungal infection in the particular populations. Methods We retrospectively reviewed pulmonary mucormycosis in patients who received allo-HSCT in our hospital from January 2010 to December 2020. A total of 21 patients fulfilled the diagnostic criteria for pulmonary mucormycosis according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Demographic and clinical data, mycological and histopathological records, and treatment and prognosis data were collected. Clinical variables were compared between survivors and nonsurvivors. The survival days of patients with and without graft-versus-host disease (GVHD) and hemoptysis were compared separately. Results Most of the recipients of allo-HSCT were male patients with a mean age of 43 years. Acute myeloid leukemia (AML) was the most common primary hematologic malignancy. Extrapulmonary involvement accounted for 28.6%, of the cases, including central nervous system (n = 5) and skin and soft tissue (n = 1). The median time to infection was 96 days after allo-HSCT. Clinical presentations were nonspecific, including fever (76.2%) and cough (85.7%), as well as dyspnea (19.0%), chest pain (38.1%), and hemoptysis (61.9%). Ground-glass infiltrates (95.0%) and nodules/masses (80%) were the most common radiographic patterns on chest CT. The most common pathogen was Rhizopus (63.2%), and breakthrough infection accounted for 90.5%. Fifteen of the patients died within one year, and the median time from diagnosis to death was 47 days. Conclusion Mucormycosis is a fatal infection disease. Opportunistic infections in recipients of allo-HSCT are mainly breakthrough infections and may have a seasonal distribution (summer and autumn) and more cases of death in autumn. The marked reversed halo sign can be seen both in the initial stage of infection and after antifungal treatment. In our case series, patients with pulmonary mucormycosis with extrapulmonary involvement 100% died within one year. There are more patients with GVHD before infection and hemoptysis in nonsurvivors than survivors within 100 days. Patients with GVHD before infection and hemoptysis have a shorter survival time than those without.