5-year Overall Survival Research Articles

Long-term Outcomes and Prognostic Factors of Gastric MALT Lymphoma.

This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum. The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS.

Trends and efficacy of omitting axillary lymph node dissection in early-stage male breast cancer with limited nodal involvement: A population-based cohort study.

The effectiveness of sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in managing early-stage male breast cancer (MBC) patients with T1-2 tumors and limited lymph node metastasis, all receiving radiotherapy, remains uncertain. This study examines trends and survival outcomes for SLNB and ALND in the United States. We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data from 2010 to 2020 for MBC patients with T1-2 tumors and 1-2 positive lymph nodes undergoing radiotherapy. Patients were classified by nodes removed (SLNB ≤5, ALND ≥10), comparing overall survival (OS) and breast cancer-specific survival (BCSS) between the groups before and after propensity score matching. Of 299 MBC patients analyzed, SLNB usage increased from 18.8% in 2010 to 61.0% in 2020. Multivariable logistic regression highlighted significant associations of SLNB use with diagnosis year, race, surgery type, positive lymph node count, and metastasis size. No significant differences in 5-year OS (77.98% SLNB vs. 85.85% ALND, p = 0.337) or BCSS (91.54% SLNB vs. 94.97% ALND, p = 0.214) were observed. Propensity score matching (96 patients per group) confirmed similar 5-year OS (83.9% for SLNB vs. 82.0% for ALND, p = 0.925) and BCSS (90.1% for SLNB vs. 96.9% for ALND, p = 0.167). SLNB and ALND provide comparable survival outcomes in early-stage MBC patients with limited lymph node metastasis undergoing radiotherapy. The increased utilization of SLNB supports its consideration to reduce surgical morbidity in selected MBC patients despite limited direct evidence.

Impact of splenectomy on long-term outcomes after gastrectomy for gastric cancer: a population-based study

BackgroundNo national studies comparing long-term survival after total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation exist. This study aimed to examine the 5-year overall survival (OS) of patients with gastric adenocarcinoma who underwent total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation in a population-based nationwide setting. MethodsThis study included all patients undergoing total or partial gastrectomy with splenectomy or spleen preservation for gastric adenocarcinoma in Finland from 2005 to 2016, with follow-up until December 31, 2019. A total of 2196 patients with gastric cancer diagnosis and total or partial gastrectomy were identified in the registries. Of these patients, 2118 were applicable for this study. Cox proportional hazard models provided hazard ratios (HRs) with 95% CIs of 5-year OS. The results were adjusted for age, sex, year of operation, comorbidities, tumor location, pathologic stage, and neoadjuvant therapy. ResultsThe observed 5-year OS rates were 38.7% in patients with no or minor spleen injury, 39.7% in patients with splenectomy due to injury, and 30.8% in patients with splenectomy due to oncologic reasons (P = .032). Patients who underwent R0 gastrectomy with splenectomy due to oncologic reasons had higher 5-year mortality (the adjusted model HR, 1.26; 95% CI, 1.01–1.56) than patients who underwent spleen preservation. ConclusionThe OS was worst in patients who underwent gastrectomy with splenectomy due to oncologic reasons, highlighting the poor prognosis in patients with advanced gastric cancer. Splenectomy due to injury does not compromise the prognosis.

Prognostic Impact of Non–Predominant Lepidic Components in Pathologic Stage I Invasive Nonmucinous Adenocarcinoma

IntroductionThis study investigated the prognostic impact of non–predominant lepidic components in invasive nonmucinous adenocarcinoma. MethodsPatients who underwent lobectomy and were diagnosed with pathologic stage I nonmucinous, non–lepidic-predominant invasive adenocarcinoma were included. Tumors were staged according to the eighth edition of TNM classification and categorized on the basis of the presence of lepidic components in the final pathology. Overall survival (OS) and recurrence-free survival (RFS) were analyzed before and after applying inverse probability of treatment weighting. Competing risk analyses for recurrence were also compared in the two groups. ResultsOf the 1270 patients, 858 (67.6%) had lepidic components (+). The pathologic stage and histologic grade were higher in the lepidic (−) group (p < 0.001, respectively). The 5-year OS and RFS were significantly worse in the lepidic (−) group than in the lepidic (+) group (OS: 88.2% versus 94.9%, p < 0.001; RFS: 79.4% versus 91.9%, p < 0.001). These trends were consistent after weighted analysis (OS: 92.4% versus 96.4%, p = 0.029; RFS: 85.6% versus 92.3%, p = 0.007). The 5-year cumulative incidence of any recurrence was 14.0% in the lepidic (−) group and 4.1% in the lepidic (+) group (p < 0.001). Multivariable Fine-Gray regression analysis found that the lepidic (+) group exhibited a lower risk of recurrence than did the lepidic (−) group (hazard ratio = 0.52, 95% confidence interval: 0.29–0.93, p = 0.031). ConclusionsIn pathologic stage I invasive nonmucinous adenocarcinoma, the presence of histologically diagnosed non–predominant lepidic components might be associated with a better prognosis after curative surgery.

Evolution of overall survival (OS) after curative-intent lung cancer surgery in a population-based Mississippi Delta cohort.

278 Background: Surgical resection is the most important curative modality for patients with lung cancer, with long-term OS influenced by both surgical quality and cancer biology. We compared surgical care and outcomes over 4 eras in the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort, an ongoing regional surgical and pathologic quality improvement (QI) dissemination and implementation project. Methods: We implemented a surgical lymph node collection kit and a novel pathology gross dissection method across 12 hospitals encompassing &gt;95% of lung cancer resections in 5 contiguous Dartmouth Hospital Referral Regions. We analyzed the MS-QSR cohort at 5-year intervals characterized by stepped-wedge implementation of specific QI interventions: Era 1 (2004-2008; baseline, no QI), Era 2 (2009-2013; quality feedback, surgical QI pilot), Era 3 (2014-2018; surgical QI implementation), and Era 4 (2019-2023; combined surgical QI and pathology QI implementation). We used standard statistical methods to compare surgical quality; Kaplan-Meier plot, log-rank test, and Cox proportional hazards model with Era 1 as reference to compare OS across eras. Results: Of 7240 resections, 14%, 31%, 29%, and 26% were performed in Eras 1-4, respectively (Table). Attainment of the stringent International Association for the Study of Lung Cancer (IASLC) definition of complete resection increased from 0% in Era 1 to 32% in Era 4; attainment of the American College of Surgeons Operative Standard 5.8 (ACS_OS 5.8), the current US definition of surgical quality, improved from 4% in Era 1 to 67% in Era 4; 120-day mortality rate decreased from 10% to 4% (p&lt;0.0001 for all comparisons). With median follow-up of 4.7, 5.5, 5.6, and 2 years for Eras 1-4, 3-year OS rates were 60%, 64%, 70%, and 79%; 5-year OS rates were 48%, 52%, 58%, and 70%, respectively (p&lt;0.0001). The Hazard Ratio (HR) for mortality decreased from 0.91 (95% CI: 0.8-0.99) in Era 2 to 0.49 (95% CI: 0.43-0.56) in Era 4. Conclusions: Surgical quality and OS sequentially improved in this diverse, high-risk population-based Mississippi Delta surgical resection cohort. We are evaluating the full range of factors associated with this striking OS improvement. Ongoing work is exploring biologic correlates to this improvement. Variable Era 1 N= 988 Era 2 N=2235 Era 3 N=2107 Era 4 N=1910 Median age (Q1, Q3) 68 (62, 74) 68 (62, 74) 68 (61, 74) 68 (61, 74) Male sex (%) 514 (52%) 1234 (55%) 1082 (51%) 977 (51%) Black race 221 (22%) 416 (19%) 450 (21%) 451 (24%) Attained ACS_OS 5.8 40 (4%) 533 (24%) 1050 (50%) 1272 (67%) IASLC complete resectionUncertain completeness 0 (0%)930 (94%) 194 (9%)1932 (86%) 435 (21%)1594 (76%) 606 (32%)1227 (64%) 120-day mortality 100 (10%) 197 (9%) 139 (7%) 72 (4%) 5-year OS 48 (45-51) 52 (50-55) 58 (56-60) 70 (66-74) HR (95% CI) Reference 0.91 (0.83-0.99) 0.75 (0.69-0.83) 0.49 (0.43-0.56)

Long-Term Outcomes in Patients With Locally Advanced Rectal Cancer Following R1 Resection After Either Induction Chemotherapy and Chemoradiotherapy or Chemoradiotherapy Alone

IntroductionTotal neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT. Patients and methodsFrom the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine. ResultsAmong 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48). ConclusionThere was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.

Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma with Deletion 17p

BackgroundDespite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. ObjectiveThe aim of this study was to evaluate real-world outcomes in patients with newly-diagnosed multiple myeloma (NDMM) with del(17p) undergoing upfront auto-HCT. Study DesignWe conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and minimal residual disease (MRD) status post-auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. ResultsOne hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34-83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1–199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. For the subset of patients with del(17p) and t(4;14), median PFS and OS were 11.5 months and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75-4.72], p<0.001), while MRD negative CR post-transplant (0.35 [0.18-0.68], p=0.002) and maintenance therapy (0.46 [0.27-0.77], p=0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18-4.17], p=0.013) and the presence of t(4;14)(2.55 [1.09-5.95], p=0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23-0.94], p=0.034) was associated with better OS. ConclusionThis study affirms del(17p) as a high-risk abnormality with unfavourable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.

HIPEC for Metastatic Gastric Cancer: Moving the Needle Towards 3-Year Survival

IntroductionPrior work has established hyperthermic intraperitoneal chemotherapy (HIPEC) administration as a safe treatment option for select patients with gastric adenocarcinoma and carcinomatosis. However, identifying patients who will maximally benefit from HIPEC remains unclear. This study assessed a single-institution experience with HIPEC for metastatic gastric cancer to identify variables associated with improved survival. MethodsA database of patients treated for metastatic gastric adenocarcinoma at MD Anderson Cancer Center from 2013-2022 was queried for patients undergoing HIPEC as part of their treatment regimen. Patients were stratified by overall survival (OS)≥36 months or <36 months and assessed along demographic and clinicopathologic variables to identify factors associated with OS≥36 months. ResultsAmong 104 patients, 1,2, and 3-year OS from diagnosis was 89%,44%, and 18%. Patients with OS≥36 months were more likely to have moderately differentiated tumors, positive cytology only (i.e. no visible carcinomatosis), and lower peritoneal cancer index (PCI) than those with OS<36 months (p=0.002, p=0.01, p=0.001,respectively). Postoperative mortality was zero in both groups. Groups did not otherwise differ with respect to demographic parameters or treatment or pathologic details. Among patients who underwent gastrectomy, those with OS<36 months had higher pathologic T and N category (p=0.003 and p=0.02, respectively). ConclusionsHIPEC may provide more durable survival benefit among patients with metastatic gastric cancer with moderately differentiated disease, low PCI, and positive cytology alone. Additionally, among patients who undergo gastrectomy, higher final pathologic T and N category are associated with worse survival. Trials are needed to compare 3-year OS rates in patients treated with HIPEC versus systemic therapy alone.

First-line treatment of severe aplastic anemia: immunosuppressive therapy plus eltrombopag versus haploidentical hematopoietic stem cell transplantation, a multicenter prospective study.

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 109/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis

PurposeThis study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN).Materials and methodsPatients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local–regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan–Meier method and log-rank tests.ResultsA total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109).ConclusionsOur study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Real world evidence study to assess incidence, treatment patterns, clinical outcomes, and health care resource utilization in early-stage, high-risk HER2-negative breast cancer in Alberta, Canada

BackgroundData are needed to improve the current understanding of the epidemiology of patients with high-risk, HER2-negative, early breast cancer (eBC) (hormone receptor positive [HR+]/HER2-negative BC and triple-negative BC [TNBC]). Patients and MethodsThis retrospective longitudinal cohort study used real-world, population-level data that included all individuals newly diagnosed with high-risk, HER2-negative eBC in Alberta, Canada, between 2010-2019. Data on treatment, laboratory results and pathology findings were collected through electronic health records and administrative databases. ResultsThe annual cumulative incidence of high-risk, HER2-negative eBC ranged from 6-9% of all incident BC cases. Individuals with TNBC were more likely to be younger, had stage II disease, grade 3 histology and received systemic therapy at a community centre (p < 0.05) compared to individuals with HR+/HER2-negative eBC. Only 14% of individuals diagnosed in 2010-2017 underwent germline BRCA testing post-diagnosis. Neoadjuvant systemic therapy was given to 37% of individuals. Adjuvant systemic therapy use increased from 77% (2012-2015) to 84% (2019). The 5-year overall survival (OS) from initiation of adjuvant systemic therapy or date of surgery (for individuals who did not receive adjuvant systemic therapy) was 77% (95% CI: 75 to 79). OS was significantly worse among individuals who were older, had grade 3 histology, had stage III disease, or had nodal involvement (p < 0.05). OS among individuals with TNBC between 2016-2019 who initiated adjuvant capecitabine was markedly worse compared to the overall cohort (2-year OS: 70% vs. 89%). ConclusionOutcomes analyses in this high-risk, HER2-negative eBC population suggest a continued unmet clinical need. Micro abstractWe characterized treatment patterns and clinical outcomes in early-stage, high-risk HER2-negative breast cancer (BC) (HR+/HER2-negative BC and triple-negative BC). Adjuvant systemic therapy use increased from 77% (2012-2015) to 84% (2019). The 5-year overall survival from initiation of adjuvant systemic therapy or date of surgery (for individuals who did not receive adjuvant systemic therapy) was 77% (95% CI: 75 to 79).

Carbon-ion radiotherapy for adenocarcinoma of the uterine cervix: clinical outcomes of a multicenter prospective registry-based study in Japan (2016–2020)

Prognoses are poorer in cases of adenocarcinoma of the uterine cervix (AUC) than of squamous cell carcinoma. Carbon-ion radiotherapy (CIRT) outcomes for AUC have been reported in retrospective or single institutional prospective studies but not prospective multicenter studies. We present the results of CIRT for AUC in a prospective multicenter study utilizing a nationwide hospital-based registry in Japan. Patients with locally advanced untreated AUC who received CIRT at 4 Japanese centers between June 2016 and April 2020 were included in this study. In the absence of organ dysfunction, up to 5 weekly 40 mg/m2 cisplatin courses were administered. The primary endpoints were 2-year overall survival (OS) and local control (LC) rates. The secondary endpoints were 2-year disease-free survival (DFS) rate and late adverse events (AEs). Forty-two patients were enrolled with a median age of 54 years (range, 34-76 years). Patients were diagnosed with Stage IIB (n=26), IIIB (n=12), or IVA (n=4) disease. The median follow-up period was 24 months. The 2-year OS, LC, and DFS rates were 97.5% (95% confidence interval [CI] 92.7-100.0%), 80.9% (95% CI 66.9-94.8%), and 64.3% (48.1-80.4%), respectively. Two patients developed Grade 3 rectum/sigmoid AE. One patient required urinary diversion surgery during a salvage operation for local tumor recurrence (Grade 3 genitourinary AE). No other Grade 3 or worse toxicities were reported. CIRT is an effective treatment for locally advanced AUC. Further research is required to validate the safety and efficacy of CIRT for AUC.

Characteristics and Survival Outcomes of Male Breast Cancer in Brazil: A Large Population-Based Study

AimsThis study evaluated the clinicopathological characteristics, treatment trends, and overall survival (OS) in male breast cancer (BC) in Sao Paulo State of Brazil. Materials and methodsMen diagnosed with invasive breast cancer between January 2000 and June 2020 were identified from Fundação Oncocentro de Sao Paulo database encompasses data pertinent to 46 million residents of the Sao Paulo State of Brazil. Patients were described according to age, education level, clinical stage, treatment modalities, and medical practice. Categorical variables were described as percentages and frequencies. Demographic, treatment factors, and OS were associated using a Cox proportional hazard regression model while accounting for different lengths of participant follow-up. The Kaplan-Meier curves were used to display survival curves. ResultsA total of 907 male BC patients were included. The age distribution at diagnosis was <51 years, 51–70 years, and >70 years in 21.5%, 51.5% and 27.0% of patients, respectively. The proportions of stages I, II, III, and IV were 19.5%, 36.6%, 31.5%, and 12.3%. For each stage I, II, III, and IV, 5- and 10-years OS were 87.9% and 77.8%, 79.9% and 58.9%, 51.6% and 24.5%, 20.0% and 5.6%, respectively. Patients who received postoperative radiotherapy experienced a significant improvement in OS (HR 0.67; 95% CI 0.53–0.84; p < 0.001). In the multivariable analysis adjusted for practice (public or private), education (low or medium/high), age, stage at diagnosis, and treatment modalities, the significant independent predictor for OS was stage at diagnosis. ConclusionMale BC tends to be diagnosed at a more advanced stage and older age at the time of diagnosis. Age and educational level did not influence survival outcomes. Stage at diagnosis and the use of postoperative radiotherapy were factors associated with improved OS.

Mechanism of Drug Resistance to First-Line Chemotherapeutics Mediated by TXNDC17 in Neuroblastomas.

The prognosis of high-risk neuroblastomas (NB) that are resistant to first-line induction chemotherapy is relatively poor. This study explored the mechanism of resistance to first-line chemotherapeutics mediated by TXNDC17 and its potential solutions in NB. The genetic and clinical data of patients with NB were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset. TXNDC17 and BECN1 expressions in NB cells were up- and downregulated by transfection with plasmids and shRNA, respectively. Autophagy-related proteins were detected by western blot. Cell viability was determined using cell proliferation and toxicity experiments. Apoptotic cells were detected using flow cytometry. Overall, 1076 pediatric and adolescent patients with NB were enrolled in this study. The 10-year overall survival (OS) rates and event-free survival (EFS) rates for the patients with a mutation of BECN1 were 37.4 ± 9.1% and 34.5 ± 8.8%, respectively. For patients with a mutation of TXNDC17, the 10-year OS and EFS were 41.4 ± 5.9% and 24.3 ± 5.1%, respectively, which were significantly lower than those in the unaltered group. The overexpression of BECN1 and TXNDC17 reduced NB sensitivity to cisplatin (DDP), etoposide (VP16), and cyclophosphamide (CTX). Autophagy mediated by BECN1 was regulated by TXNDC17, and this process was involved in the resistance to DDP, VP16, and CTX in NB. Suberoylanilide hydroxamic acid (SAHA) can enhance the sensitivity and apoptosis of NB cells to chemotherapeutics by inhibiting TXNDC17, ultimately decreasing autophagy-mediated chemoresistance. Acquired resistance to first-line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

Living donor liver transplantation for hepatocellular carcinoma using expanded criteria and alpha-fetoprotein threshold of 1000 ng/mL

BackgroundNew guidelines propose a minimum 5-year survival of 60% for hepatocellular carcinoma (HCC) with living donor liver transplantation (LDLT). This study aimed to evaluate the 5- and 10-year survival rates after transplantation for the expanded criteria for HCC. MethodsThis single-center retrospective cohort study included 208 patients who underwent LDLT for the expanded criteria (the largest tumor diameter of ≤10 cm, any tumor number, and alpha-fetoprotein [AFP] level of <1000 ng/mL) and analyzed 5- and 10-year overall survival (OS) and recurrence risk (RR) rates. ResultsWith a median follow-up of 65.1 months (IQR, 19.1–80.2), the 5- and 10-year OS and RR rates were 67.0% and 61.0% and 20.5% and 22.5%, respectively. The largest tumor diameter of >6 cm (hazard ratio [HR], 3.7; 95% CI, 1.7–8.2; P = .001) and AFP level of >400 ng/mL (HR, 4.0; 95% CI, 1.8–9.0; P = .001) were predictors of recurrence. Patients outside the Milan criteria (MC) were grouped into low- and high-risk HCC based on tumor size and AFP level. For low-risk HCC (tumor size of <6 cm, any tumor number, and AFP level of <400 ng/mL), the 5-year RR was comparable to the MC and increased the transplant pool by 35.7% (P > .5). The median number of tumors and the rate of microvascular invasion in the high-risk group, low-risk group, and MC were 2.0 (1.0–3.2), 4.0 (2.0–5.0), and 1.0 (1.0–2.0) (P < .001) and 72.2% (13/18), 44.0% (22/50), and 22.8% (32/140) (P < .001), respectively. ConclusionThe expanded criteria met the benchmark for 5-year survival. LDLT for the low-risk HCC in the expanded criteria was associated with an acceptable RR.

Survival and Patterns of Relapse of Cutaneous Squamous Cell Carcinoma With Large Nerve Perineural Spread After Skull Base Surgery and/or Radiation Therapy

The aim of our study was to evaluate survival and patterns of relapse for patients with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC), who have undergone curative intent skull base surgery and/or radiation therapy. In addition, we modified the classification of zone 2 disease into 2a and 2b and reported the respective outcome. A review of a prospective database of patients who received diagnoses of PNS of cSCC and were treated with curative intent skull base surgery and/or radiation therapy between the years of 2013 and 2020 was conducted. Kaplan-Meier methods were used to estimate relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Cox proportional hazard modeling was performed to test associations between patient factors and survival outcomes. Eighty patients with a median follow-up of 36 months were included in the study. The 5-year RFS was 61% (95% CI, 48%-71%), the DSS was 77% (95% CI, 63%-86%), and OS was 67% (95% CI, 53%-78%). In multivariable modeling, involvement of 2 or more nerves was strongly associated with worse 5-year RFS (HR, 4.0; P ≤ .001), DSS (HR, 4.5; P = .004), and OS (HR, 4.3; P = .002). Age group (≥65 years) (HR, 5.1; P = .010) and immune compromise (HR, 10.7; P = .001) were strongly associated with worse OS but not DSS or RFS. The majority of relapses (60%) occurred at the local skin sites. Our study demonstrated surgery followed by radiation therapy was safe and effective in the management of cSCC with PNS. We did not detect a difference in outcome between zones 2a and 2b though further study is required. The most common mode of relapse was at the skin epidermis and/or adjacent dermis highlighting the importance of adequate local skin dose delivery.

Clinicopathologic Features and Surgical Management in Vulvovaginal Melanoma – A Retrospective Single Center Study

Background and AimsVulvovaginal melanoma is a rare malignancy characterized with poor prognosis. The aim of this study was to review vulvovaginal melanoma patients treated in Helsinki University Hospital. Objective was to evaluate the clinicopathologic features, treatment and factors affecting outcome. MethodsSingle-center retrospective review on patients treated between 2001 and 2021 was conducted. Data were collected from medical records. Clinicopathologic features, treatment, survival, and prognostic factors were analyzed. ResultsA total of 21 patients were included in the analysis. Localization was vulvar in 86% (n=18) and vaginal in 14% (n=3). Median age at diagnosis was 80 years. Initial treatment included surgery in 18 patients (86%); wide local excision in 19%, radical excision in 62%, and pelvic exenteration in 4.8%. Negative margins were achieved in 83% (n=15). Eleven (52%) patients underwent inguinal treatment: sentinel lymph node biopsy in 33%, direct lymphadenectomy in 14%, and both in 4.8%. Nine patients experienced melanoma recurrence. Recurrences were locoregional (n=1), distant (n=4), and both locoregional and distant (n=4). Median disease-free survival was 18.9M and median overall survival (OS) was 36.5M. 5-year relative OS was 20%. Melanoma was cause of death for seven patients (33%). Vaginal localization tended to worsen prognosis. Nodal status was the only melanoma characteristic significantly associated with survival. Surgical radicality did not affect survival. ConclusionsVulvovaginal melanoma is associated with an extremely poor survival and high rates of recurrence, primarily involving distant metastasis. In local control, wide local excision seems to be viable alternative to more radical surgery. Nodal status is a key prognostic factor emphasizing the importance of further research into the applicability of sentinel lymph node biopsy for vulvovaginal melanoma.

Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide.

This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. The median observation period was 46.4months, and the median age of patients at diagnosis was 71years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2ng/mL in a median time of 4.7months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9months. These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

Para-aortic lymph node dissection following neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer with extensive lymph node metastasis.

D2 and para-aortic lymph node dissection (PAND) following neoadjuvant chemotherapy (NAC) are reportedly effective for gastric cancer (GC) with extensive lymph node metastasis (ELM), such as para-aortic nodal metastasis or bulky nodal metastasis, around the major perigastric arteries. However, type 4 and large type 3 tumors were excluded from previous studies, as they are considered special subtypes that easily spread to the peritoneum. Whether or not PAND contributes to the survival of type 4 or large type 3GC with ELM is thus unclear. This study examined patients who underwent radical gastrectomy with D2 resection and PAND following NAC between 2002 and 2019. Patients were classified into the normal-type group and the type 4 or large type 3 group. The overall survival (OS) and prognostic factors were investigated. Forty-nine patients were examined and classified into the normal-type group (34 patients) and type 4 or large type 3 group (15 patients). The 5-year OS rates of the normal-type and type 4 or large type 3 groups were 55.5% and 26.7%, respectively. Type 4 or large type 3 tumors were an independent risk factor for a poor prognosis in the multivariate analysis (hazard ratio: 2.506, 95% confidence interval: 1.111-5.650, and p=0.027). The prognosis of type 4 or large type 3GC with ELM treated with radical gastrectomy with D2 and PAND after NAC was poor. Type 4 or large type 3 GC with ELM should be treated using a different strategy than the normal type with ELM.