Post-recurrence Treatment Research Articles

Long-Term Survey of Japanese Children with Recurrent Nephroblastoma: A Report from Japan Children’s Cancer Group

In prospective Japanese studies of pediatric renal tumors, 5-year event-free survival and overall survival (OS) for patients with nephroblastoma ranges from 75–90% and 89–97%, respectively. However, treatments strategies for recurrent nephroblastoma in Japanese patients remain unclear. This retrospective study aimed to inform the development of treatment strategies by analyzing the long-term results and side effects of salvage therapies for recurrent nephroblastoma in Japan. A questionnaire survey involving 41 institutions (74 patients) collected clinical data on recurrent cases reported to the Renal Tumor Committee of the Japan Children’s Cancer Group. Survey forms from 54 cases were evaluated. Median time to recurrence was 9.5 months among 51 patients without underlying disorders. Recurrence occurred at lung-only in 18 patients and at other sites in 33. The 5-year OS for all 51 patients was 70.6%, with recurrent disease causing death in 15 patients and one patient dying from treatment-related complications. Patients with lung-only recurrence had higher 5-year OS rates than those with other-site recurrence. Initial chemotherapy intensity also affected prognosis, with lower intensity associated with higher 5-year OS. In 17 survivors with lung-only recurrence, the most frequent treatment approach combined chemotherapy, surgery and radiotherapy. Conventional chemotherapy included platinum-containing regimens and/or Regimen I-based treatment containing cyclophosphamide and etoposide. Salvage therapies showed remarkable effectiveness for patients with lung-only recurrence or low intensity of the initial chemotherapy, highlighting the need to standardize prospective studies for post-recurrence treatment and identify risks of late complications for long-term survivors.

470. INTENSIVE EARLY SURVEILLANCE FOLLOWING ESOPHAGECTOMY IDENTIFIES DISTINCT PATTERNS OF RECURRENCE

Abstract Background There remains a lack of consensus about the protocol for follow-up following esophagectomy. Some centers will utilize a purely radiological approach to follow-up, while others will include routine endoscopy and blood markers. Furthermore, the frequency of follow-up is debated, though many centers will follow-up every 3 months due to the high recurrence rate in the first year. We follow patients every 3 months for the first year, every 6 months for the next year, then yearly to 5 years, solely with CT scans unless symptoms indicate endoscopy. We sought to examine our recurrence rate and survival using this follow-up protocol. Methods We reviewed our prospectively collected database for recurrence following esophagectomy in patients operated from March 2018 to May 2022. Consenting patients >18 years of age who underwent esophagectomy were included. Demographics including age, sex, and BMI, tumor factors including pathologic stage, tumor regression grade, and neoadjuvant therapy and post-recurrence treatment data were collected. Results We identified 190 patients who underwent esophagectomy and 69 patients had a recurrence. Patients with recurrence were younger (61.3 +/- 10.2 vs 66.4 +/- 10.1, p=0.001), were more likely pT3 (59.4% vs 36.4%, p=0.013) and have a tumor regression grade of 3 (27.5% vs 7.4%, p=0.002). There was no difference between patients with R1 resections vs R0 (5.8% vs 6.6%, p=0.824). Most recurrences were identified on CT scan (95.8%). For patients who recurred within 3 months, the mean time from operation to death was 9.11 months. Patients who recurred between 3-6mo, 6-9mo, and 9-12mo died at 17.1mo, 15.7mo, and 17.5mo following surgery, respectively. Patients who recurred in the next year died around 40 months from surgery. Conclusion As with other reports in the literature, recurrence is highest in the first year after esophagectomy. Patients recurring in the first 3 months had a short survival following esophagectomy and may represent missed micrometastatic disease at staging. Interestingly, patients who recurred between 3-12 months all had a similar time to death from the date of operation, suggesting lead-time bias for those detected at 3-6months. Early and later recurrence appear to have distinct biological behaviours. With improved and tailored adjuvant therapies, earlier detection may yet be beneficial and will require further study.

Postrecurrence Treatment in Neoadjuvant or Adjuvant FDA Registration Trials

In oncology randomized clinical trials, suboptimal access to best available care at recurrence (or relapse) may affect overall survival results. To assess the proportion and the quality of postrecurrence treatment received by patients enrolled in US Food and Drug Administration (FDA) registration trials of systemic therapy in the adjuvant or neoadjuvant setting. For this systematic review, all trials leading to an FDA approval from January 2018 through May 2023 were obtained from the FDA website and drug announcements. Randomized clinical trials of an anticancer drug in the neoadjuvant or the adjuvant setting were included. Trials of supportive care treatment and treatments given in combination with radiotherapy were excluded. Information abstracted for each trial included tumor type, setting, phase, type of sponsor, reporting and assessment of postrecurrence, and overall survival data. A total of 14 FDA trials met the inclusion criteria. Postrecurrence data were not available in 6 of 14 registration trials (43%). Of the 8 remaining trials, postrecurrence treatment was assessed as suboptimal in 6 (75%). Overall, only 2 of 14 trials (14%) had data assessed as appropriate. This systematic review found that 43% of randomized clinical trials of anticancer treatment in the adjuvant or neoadjuvant context failed to present any assessable postrecurrence treatment data. In instances in which these data were shared, postrecurrence treatment was suboptimal 75% of the time. The findings suggest that regulatory bodies should enforce rules stipulating that patients have access to the best standard of care at recurrence.

Real-world clinical characteristics and treatment patterns among people with hepatocellular carcinoma in the United States (US) treated with resection or ablation.

436 Background: Treatment guidelines for early-stage hepatocellular carcinoma (eHCC) include therapies with curative intent comprising three primary strategies: liver transplantation, surgical resection, or ablation (for small lesions). However, many people experience HCC recurrence, with recurrence rates of up to approximately 80% within 5 years after resection. Furthermore, contemporary insights into the eHCC treatment landscape and post-recurrence treatment patterns in the real-world setting are lacking. This study was designed to assess demographic and clinical characteristics and treatment patterns for people with HCC who received resection or ablation as a proxy for defining early-stage disease. Methods: This was a retrospective observational cohort study of adults with HCC treated with resection or ablation in the US, conducted using linked electronic health records and healthcare claims from Optum’s de-identified Market Clarity Data. Index date was the date of the first observed resection or ablation between July 2016 and March 2021. Baseline characteristics were assessed in the 6-month period prior to index, and patients (pts) were followed until end of continuous enrolment in a medical and pharmacy plan, death, or data cut-off (September 2022), whichever occurred first. Demographic and clinical characteristics and treatment patterns, including subsequent treatments, were described. Results: A total of 649 pts met the study criteria and were included in the analyses. The median duration of follow-up was 23.0 months (range: 0.03–74.55 months). The mean age at index was 64.1 years (median 64.0 years), with a majority male gender (72.9%) and White race (65.5%). A total of 385 pts (59.3%) underwent ablation only, 242 pts (37.3%) underwent resection only, and 22 pts (3.4%) underwent both procedures at index. Transarterial embolization alone was received by 57 (8.8%) pts and was the most common embolization procedure received during follow-up, followed by transarterial chemoembolization alone in 46 (7.1%) pts and transarterial radioembolization in 46 (7.1%) pts. A total of 88 (13.6%) pts received systemic therapies for HCC (tyrosine kinase inhibitors, programmed cell death protein-1/programmed cell death-ligand 1/cytotoxic T-lymphocyte-associated antigen 4 inhibitors, or angiogenesis inhibitors) during follow-up. Conclusions: In this real-world cohort, ablation was the most received curative intent therapy for HCC. Among treatments received during follow-up, locoregional therapies were used most often, followed by systemic therapies. Although limited by its retrospective, observational nature, short duration of follow-up, and availability of data in the database, the results of this analysis provide a contemporary landscape of early-stage treatments for HCC in the real-world setting.

Early versus Late Recurrence of Hepatocellular Carcinoma after Microwave Ablation: Patterns, Treatments, and Post-Recurrence Survival

Introduction: Recurrence after microwave ablation (MWA) has not been extensively studied. We aimed to investigate the patterns, treatments, and survival of patients with hepatocellular carcinoma (HCC) who experienced early and late recurrence after MWA. Methods: This retrospective study included patients with HCC recurrence after MWA as the initial treatment from January 2008 to December 2021. Recurrence patterns, treatments, and outcomes between patients with early and late HCC recurrence were compared. Prognostic factors of post-recurrence survival (PRS) were identified by multivariable Cox regression analyses. Results: Among 222 patients, 128 developed early recurrence (≤2 years after MWA) and 94 had late recurrence (>2 years). Majority of the recurrent HCC were intrahepatic-only recurrence, within the Milan criteria, and received potentially curative treatment. No significant differences in the recurrence patterns, vascular invasion, tumor staging, post-recurrence treatments, or median PRS (35.0 vs. 33.0 months, p = 0.523) were identified between patients with early and late recurrence. Multivariable analyses suggested that multiple tumor number (hazard ratio [HR]: 1.54; 95% CI: 1.03–2.30, p = 0.038), extrahepatic recurrence (HR: 2.14, 95% CI: 1.16–3.92, p = 0.015), vascular invasion (HR: 2.37, 95% CI: 1.18–4.76, p = 0.038), and higher ALBI grade (HR: 2.18, 95% CI: 1.54–3.08, p < 0.001) were independent risk factors of worse PRS, while curative treatment after recurrence (HR: 0.59, 95% CI: 0.38–0.92, p = 0.020) was associated with better PRS. Conclusions: No differences in recurrence patterns, post-recurrence treatments, or PRS were found between HCC patients with early and late recurrence following MWA. Tumor burden and patients’ liver function reserve should be considered to decide the optimal post-recurrence treatment after MWA.

Progression of Site-specific Recurrence of Pancreatic Cancer and Implications for Treatment.

To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment. Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains. This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes. Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression. Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.

The Prognostic Value of Oligo-Recurrence Following Esophagectomy for Esophageal Cancer.

The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center

BackgroundRecurrence is frequently observed after esophageal cancer surgery, with dismal post-recurrence survival. Neoadjuvant chemoradiotherapy followed by esophagectomy is the gold standard for resectable esophageal tumors in the Netherlands. This study investigated the recurrence patterns and survival after multimodal therapy. MethodsThis retrospective cohort study included patients with recurrent disease after neoadjuvant chemoradiotherapy followed by esophagectomy for an esophageal adenocarcinoma in the Amsterdam UMC between 01 and 01–2010 and 31-12-2018. Post-recurrence treatment and survival of patients were investigated and grouped by recurrence site (loco-regional, distant, or combined loco-regional and distant). ResultsIn total, 278 of 618 patients (45.0%) developed recurrent disease after a median of 49 weeks. Thirty-one patients had loco-regional (11.2%), 145 distant (52.2%), and 101 combined loco-regional and distant recurrences (36.3%). Post-recurrence survival was superior for patients with loco-regional recurrences (33 weeks, 95%CI 7.3–58.7) compared to distant (12 weeks, 95%CI 6.9–17.1) or combined loco-regional and distant recurrent disease (18 weeks, 95%CI 9.3–26.7). Patients with loco-regional recurrences treated with curative intent had the longest survival (87 weeks, 95%CI 6.9–167.4). ConclusionRecurrent disease after potentially curative treatment for esophageal cancer was most frequently located distantly, with dismal prognosis. A subgroup of patients with loco-regional recurrence was treated with curative intent and had prolonged survival. These patients may benefit from intensive surveillance protocols, and more research is needed to identify these patients.

The treatment efficacy and prognosis of each treatment in early postoperative recurrence of esophageal squamous cell carcinoma.

Various treatments are used for early postoperative recurrence of esophageal cancer, which has a poor prognosis. We evaluated the differences in outcomes and prognoses of each treatment modality between patients with early and late recurrence. Early and late recurrence were defined as recurrence within and after six postoperative months, respectively. Of the 351 patients with esophageal squamous cell carcinoma who underwent R0 resection esophagectomy, 98 experienced postoperative recurrence (early recurrence, n = 41; late recurrence, n = 57). We evaluated the characteristics of patients with early and late recurrence and compared their treatment responses and prognoses. Regarding treatment responses for chemotherapy or immunotherapy, the objective response rate was not significantly different between the early- and late-recurrence groups. For chemoradiotherapy, the objective response rate was significantly lower in the early-recurrence group than in the late-recurrence group. The overall survival was significantly worse in the early-recurrence group than in the late-recurrence group. An analysis by treatment type showed that the early-recurrence group had significantly worse overall survival for chemoradiotherapy, surgery, and radiotherapy than the late-recurrence group. Patients with early recurrence had particularly poor prognoses with worse post recurrence treatment efficacy than those with late recurrence. The differences in the treatment efficacy and prognosis were particularly pronounced for local therapy.

Effect of High-Versus Low-Frequency of Abdominopelvic Computed Tomography Follow-Up Testing on Overall Survival in Patients With Stage II Or III Colon Cancer

BackgroundIntensive surveillance of colon cancer by using the abdominopelvic computed tomography (AP-CT) is common in real world practice; however, it is still unclear whether high-frequency surveillance using AP-CT in patients with these risk factors is superior to that in the low-frequency surveillance. Patients and MethodsWe retrospectively reviewed 1803 patients with stage II-III colon cancer receiving curative surgery between January 1, 2005 to December 31, 2015. We evaluated the average scan-to-scan intervals of postoperative AP-CT testing and assigned patients with an interval of 5 to 8 and 9 to 13 months to the high-frequency (HF) and low-frequency (LF) groups, respectively. The cutoff value of preoperative and postoperative CEA levels was 5 ng/mL. We also applied propensity score matching (PSM) and inverse probability of treatment weighting to adjust clinicopathologic differences between the 2 groups. ResultsWe matched 1:1 for each surveillance group yielding a cohort of 776 matched patients. After PSM, Baseline demographics were overall well balanced between 2 groups. Stage III (OR, 2.00; 95% Confidence interval [CI], 1.21-3.30) and postoperative CEA elevation (OR, 2.30; 95% CI, 1.08-4.92) were independent risk factors of recurrence in multivariate analyses. Patient in the HF group had more surgery plus chemo- or radiotherapy as postrecurrence treatment than patient in the LF group (46.2% vs. 23.1%, P = .017). This trend was retained after PSM, although it is not significant (44.4% vs. 23.1%, P = .060). However, survival outcomes of high-frequency AP-CT surveillance were not superior to those of low-frequency surveillance in all subgroups, including stage III (HR 0.99, 95% CI 0.40-2.47) and postoperative CEA elevation (HR 1.36, 95% CI 0.45-4.11). ConclusionHigh-frequency AP-CT testing is associated with a higher proportion of surgery plus chemo- or radiotherapy as postrecurrence treatment, without improvement in 5-year overall survival.

Association between surveillance imaging and survival outcomes in small bowel neuroendocrine tumors

Surveillance guidelines following the resection of small bowel neuroendocrine tumors (SB-NETs) are inconsistent. We evaluated the impact of surveillance imaging on SB-NET recurrence and overall survival (OS). Patients with completely resected SB-NETs referred to a provincial cancer center (2004-2015) were reviewed. Associations between imaging frequency, recurrence, post-recurrence treatment, and OS were determined using univariate and Cox-regression analyses. Among 195 completely resected SB-NET patients, 31% were ≥70 years, 43% were female, and 80% had grade 1 disease. Imaging frequency was predictive of recurrence (hazard ratio 2.52, 95% confidence interval 1.84-3.46, p < 0.001). 72% underwent interventions for recurrent disease. Patients who were treated for the recurrent disease had comparable OS to those who did not recur (median 152 vs. 164 months; p = 0.25). Imaging frequency was not associated with OS in those with treated recurrent disease (p = 0.65). Patients who recurred underwent more computerized tomography(CT) scans than those who did not recur (CT: 1.47 ± 0.89 vs. 1.02 ± 0.81 scans/year, p < 0.001). Detection of disease recurrence was 5%-7% per year during the first 6 years of surveillance and peaked at 17% in Year 9. Less frequent imaging over a longer duration should be emphasized to capture clinically relevant recurrences that can be treated to improve OS.

Real-world adjuvant chemotherapy treatment patterns and outcomes over time for resected stage II and III colorectal cancer.

The administration of adjuvant chemotherapy (AC) to colorectal cancer (CRC) patients in Australia and impact of recent trial data has not been well reported. We aim to evaluate temporal trends in AC treatment and outcomes in real-world Australian patients. CRC patients were analyzed from 13 hospitals, stratified by stage (II or III) and three 5-year time periods (A: 2005-2009, B: 2010-2014, C: 2015-2019). Stage III was further stratified as pre- and post publication of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration (March 2018). AC prescription, time-to-recurrence (TTR), and overall survival (OS) was compared across the time periods. Of 3977 identified patients, 1148 (stage II: 640, stage III: 508), 1525 (856 vs. 669), and 1304 (669 vs. 635) were diagnosed in Period A, B, and C, respectively. Fewer patients in Period C received AC compared to Period B in stage II (10% vs. 15%, p <.01) and III (70% vs. 79%, p <.01). Post-IDEA, the proportion of patients receiving ≤3 months of oxaliplatin-based AC increased (45% vs. 13%, p <.01). The proportion of patients who remained recurrence free at 3 years was similar between time periods in stage II (A: 89% vs. B: 88% vs. C: 90%, p = .53) and stage III (72% vs. 76% vs. 72%, p = .08). OS significantly improved for stage II (80%-85%, p = .04) and stage III (69%-77%, <.01) from period A to B. AC use has moderately decreased over time with no impact on recurrence rates. Improved survival in more recent years despite similar recurrence rates may be related to improved baseline staging, better postrecurrence treatment, and reduced noncancer-related mortality.

SA6 Challenges in Economic Modelling of Adjuvant Cancer Therapy for Health Technology Assessments

Economic modelling of adjuvant cancer therapy is subject to several challenges, including post-recurrence treatment options and limited overall survival (OS) data, reducing applicability of traditional oncology approaches, such as partitioned-survival models. This study aimed to identify the most appropriate modelling approach for adjuvant therapies in the UK setting.

Recurrence Pattern Comparing Preoperative Chemoradiotherapy and Preoperative Chemotherapy with Docetaxel plus 5-Fluorouracil and Cisplatin for Advanced Esophageal Cancer

Background: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF). Methods: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases. Results: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients. Conclusions: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence.

375. PATTERNS OF RECURRENT DISEASE AFTER NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGEAL CANCER SURGERY WITH CURATIVE INTENT

Abstract Recurrence is frequently observed in patients after esophageal cancer surgery and post-recurrence survival is dismal. Neoadjuvant chemoradiotherapy (nCRTx) followed by esophagectomy is the gold standard of care for resectable esophageal tumors in The Netherlands. This study investigated the recurrence patterns and survival in patients after nCRTx and esophagectomy. This retrospective cohort study included data from a prospectively maintained database of patients with recurrent disease after nCRTx followed by esophagectomy in the Amsterdam UMC between 01-01-2010 and 31-12-2018. Post-recurrence treatment and survival were investigated for patients specified for tumor histology (adenocarcinoma [AC] or squamous cell carcinoma [SCC]) and by recurrence site (loco-regional, distant, or combined loco-regional and distant). In total, 340 of the 803 patients included (42.3%) after nCRTx and esophagectomy developed a recurrent disease at a median of 49 and 51 weeks postoperatively, for patients with an AC or SCC, respectively. Fifty patients had loco-regional (14.7%, AC:11.2%/n = 31, SCC:32.2%/n = 19), 167 patients distant (49.1%, AC:52.3%/n = 145, SCC:33.9%/n = 20) and 122 patients had combined recurrences (35.9%, AC:36.5%/n = 101, SCC:33.9%/n = 20). Post-recurrence survival was superior for AC patients with loco-regional (33 weeks, 95%CI:7.3-58.7) compared to AC patients with distant (12 weeks, 95%CI 6.9-17.1) or combined recurrences (18 weeks, 95%CI:9.3-26.7). AC patients with loco-regional recurrences receiving curative intent treatment had the longest survival (87 weeks, 95%CI:6.9-167.4). Most esophageal cancer recurrences after curatively intended treatment were located at distant or combined loco-regional and distant sites, with limited survival prospects. A subgroup of patients with loco-regional recurrence can be treated with curative intent and has prolonged survival. How to identify these patients needs to be investigated, as they may benefit from close postoperative surveillance.

Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment.

Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. Risk factors for LEC were defined as a short baseline 6-min walk distance (<400m), older age (≥75years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27-2.92, 2.01-5.58, 3.64-23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

Genomic Analysis Focusing on RUNX1-RUNX1T1 in Japanese Patients with AML: HM-Screen-Japan 01

Genomic Analysis Focusing on RUNX1-RUNX1T1 in Japanese Patients with AML: HM-Screen-Japan 01

Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy.

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263–0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521–0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137–0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897–0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.

Prognostic Nomograms for Patients with Hepatocellular Carcinoma After Curative Hepatectomy, with a Focus on Recurrence Timing and Post-Recurrence Management.

BackgroundPrognoses of patients with hepatocellular carcinoma (HCC) after curative hepatectomy remain unsatisfactory because of the high incidence of postoperative recurrence. Published predictive systems focus on pre-resection oncological characteristics, ignoring post-recurrence factors.PurposeThis study aimed to develop prognostic nomograms for 3- and 5-year overall survival (OS) of patients with HCC after curative hepatectomy, focusing on potentially influential post-recurrence factors.Patients and MethodsClinicopathological and postoperative follow-up data were extracted from 494 patients with HCC who underwent curative hepatectomy between January 2012 and June 2019. Early recurrence (ER) and late recurrence (LR) were defined as recurrence at ≤2 and >2 years, respectively, after curative hepatectomy. Nomograms for the prediction of 3- and 5-year OS were established based on multivariate analysis. The areas under time-dependent receiver operating characteristic curves (AUCs) for the nomograms were calculated independently to verify predictive accuracy. The nomograms were internally validated based on 2000 bootstrap resampling of 75% of the original data.ResultsIn total, 494 patients with HCC who underwent curative hepatectomy met the eligibility criteria. Cox proportional hazard regression analysis identified factors potentially influencing 3- and 5-year OS. Multivariate analysis indicated that patient age, Hong Kong Liver Cancer stage, γ-glutamyl transferase (γ-GGT) level, METAVIR inflammation activity grade, ER and post-recurrence treatment modality were influencing factors for 3-year OS (AUC, 0.891; 95% CI, 0.8364–0.9447). γ-GGT > 60 U/L, hepatectomy extent, LR and post-recurrence treatment modality were influencing factors for 5-year OS (AUC, 0.864; 95% CI, 0.8041–0.9237). Calibration plots showed satisfactory concordance between the predicted and actual observation cohorts.ConclusionWe propose new prognostic nomograms for OS prediction with a focus on the differentiation of recurrence timing and post-recurrence management. These nomograms overcome the shortcomings of previous predictive nomograms and significantly improve predictive accuracy.

Comprehensive comparison of clinicopathological characteristics, treatment, and prognosis of borderline resectable pancreatic cancer according to tumor location

BackgroundThe prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. MethodsWe retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. ResultsA total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). ConclusionsIn our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.