5-year Relapse-free Survival Rates Research Articles

Survival outcomes and functional results of VOLTAGE-A: Preoperative chemoradiotherapy (CRT) and consolidation nivolumab (nivo) in patients (pts) with both microsatellite stable (MSS) and microsatellite instability–high (MSI-H) locally advanced rectal cancer (LARC).

108 Background: In VOLTAGE-A, CRT (50.4 Gy with capecitabine of 1,650 mg/m2) followed by five cycles of consolidation Nivo (240 mg q2 weeks [W]) and radical surgery showed 30% of pathological complete response (pCR) in pts with MSS and 60% in MSI-H T3–4 NanyM0 LARC. Here, we report survival outcomes and functional results. Methods: All 39 MSS and 5 MSI-H pts were included in the VOLTAGE-A from Jan 2017 to Oct 2019. Survival outcomes, late adverse events, and patient-reported outcome measurements for urogenital and anal functions were analyzed. Urinary function was evaluated using the International Prostate Symptom Score (I-PSS) periodically at 1W, 1, 3, 6, and 12 months (M), postoperatively. Sexual function in sexually active male pts was evaluated using the International Index of Erectile Function (IIEF) score at 3, 6, and 12M, postoperatively. Anal function was evaluated using the Wexner score, low anterior resection syndrome (LARS) score, and fecal incontinence severity index (FISI) score at 1-year post-surgery. All functional scores were evaluated preoperatively. Results: With a median follow-up of 44.8M (range, 25.7-58.9M), the 3-year relapse-free survival (RFS) and 3-year overall survival (OS) rates were respectively 79.5% and 97.4% in MSS, and 100% each in MSI-H pts. Of the MSS pts, those with pCR, clinical CR (cCR) according to the MSKCC criteria, high PD-L1 expression (tumor proportion score [TPS] ≥1%), and CD8/eTreg ratios of ≥2.5 had a trend of better 3-year RFS and OS than those without. During the follow-up period, one patient developed CTCAE grade 3 immune-related colitis, which was diagnosed 20M after the last dose of Nivo. Postoperative functional results were acceptable in both populations; pre-surgical median I-PSS scores were 3, whereas postsurgical values were 5 (1W), 5.5 (1M), 5 (3M), 4 (6M), and 4 (12M); median IIEF score was 20 at pre-surgery and 6 (3M), 6 (6M), and 8 (12M) at post-surgery; median scores of Wexner, LARS, and FISI were 2, 23, and 7 at pre-surgery, and 9, 30, and 17 at 1-year post-surgery, respectively. Conclusions: Preoperative CRT followed by Nivo showed promising survival outcomes in both MSS and MSI-H LARC pts. The therapeutic effect of pCR, cCR, and certain biomarkers analyzed by pre-CRT samples could be used as prognostic predictors in MSS pts. Clinical trial information: NCT02948348 .[Table: see text]

Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2

To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML). TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors. The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049). In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Older age is not a negative factor for video-assisted thoracoscopic lobectomy for pathological stage I non-small cell lung cancer: a single-center, retrospective, propensity score-matching study.

Video-assisted thoracoscopic surgery (VATS) has changed the surgical approach to non-small cell lung cancer (NSCLC) dramatically. The current study compares the outcomes of older and younger patients who underwent VATS lobectomy for NSCLC. In total, 424 eligible patients with pathological stage I NSCLC underwent VATS lobectomy between 2007 and 2017. Patients were classified into two groups (< 75 and ≥ 75years old), after which propensity score-matching was performed. After matching, 143 patients were identified. No significant difference in postoperative complication rates was observed; however, the ≥75-year-old group had a longer postoperative hospital stay (p = 0.001). The 5-year overall survival, relapse-free survival, and lung cancer-specific survival rates of the < 75- and ≥ 75-year-old groups were 87.1% vs. 85.6% (p = 0.537), 82.1% vs. 79.0% (p = 0.531), and 93.5% vs. 92.7% (p = 0.832), respectively. Despite the longer postoperative recovery following VATS lobectomy, the short- and long-term outcomes of older patients did not differ from those of younger patients. Thus, for early-stage NSCLC, older age alone was not a negative factor for lobectomy performed via minimally invasive surgery. Naturally, the systemic condition of this population must be evaluated carefully before surgery.

Value of the Tumor-Stroma Ratio and Structural Heterogeneity Measured by a Novel Semiautomatic Image Analysis Technique for Predicting Survival in Patients With Colon Cancer.

The tumor-stroma ratio and intratumor stromal heterogeneity have been identified as prognostic factors for several carcinomas. Recent advancements in image analysis technologies and their application to medicine have enabled detailed analysis of clinical data beyond human cognition. This study aimed to investigate the tumor-stroma ratio and intratumor stromal heterogeneity measured using a novel objective and semiautomatic method with image analysis. A retrospective cohort design. Single institution. This study included patients who underwent curative colectomy for colon cancer. The survival analyses between tumor-stroma ratio or intratumor stromal heterogeneity high and low groups after colectomy were assessed in multivariate analyses. Two hundred patients were divided into 2 groups based on the median tumor-stroma ratio and intratumor stromal heterogeneity values. The 5-year overall survival and relapse-free survival rates after colectomy significantly differed between the high and low tumor-stroma ratio or intratumor stromal heterogeneity groups. Multivariate analysis identified low tumor-stroma ratio (HR: 1.90, p = 0.03) and high intratumor stromal heterogeneity (HR: 2.44, p = 0.002) as independent poor prognostic factors for relapse-free survival. The tumor-stroma ratio and intratumor stromal heterogeneity correlated with the duration from curative surgery to recurrence. Furthermore, postoperative recurrence within 2 years was predicted with higher accuracy by using the tumor-stroma ratio or intratumor stromal heterogeneity than by using the pathological stage. In a validation cohort, interobserver agreement was assessed by 2 observers, and Cohen's κ coefficient for the tumor-stroma ratio (κ value: 0.70) and intratumor stromal heterogeneity (κ value: 0.60) revealed a substantial interobserver agreement. This study was limited by its retrospective, single-institution design. Tumor-stroma ratio and intratumor stromal heterogeneity calculated using image analysis software have potential as imaging biomarkers for predicting the survival of patients with colon cancer after colectomy. See Video Abstract at http://links.lww.com/DCR/C114 . ANTECEDENTES:La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral han sido identificados como factores pronósticos para varios tipos de carcinomas. Los avances recientes en cuanto a las tecnologías de análisis de imágenes y sus aplicaciones en la medicina, han permitido un análisis detallado de los datos clínicos más allá del conocimiento humano.OBJETIVO:Investigar la relación del estroma tumoral y la heterogeneidad del estroma intratumoral calculados mediante un nuevo método objetivo y semiautomático para el análisis de imágenes.DISEÑO:Diseño de cohorte retrospectivo.AJUSTES:Institución única.PACIENTES:Pacientes sometidos a colectomía curativa por cáncer de colon.PRINCIPALES MEDIDAS DE RESULTADO:Los análisis de supervivencia entre la relación del estroma tumoral o la heterogeneidad del estroma intratumoral entre los grupos con valores altos y bajos tras la colectomía, fueron evaluados en análisis multivariados.RESULTADOS:Fueron divididos 200 pacientes en dos grupos basados en la mediana de la proporción con respecto a los valores del estroma tumoral y la heterogeneidad del estroma intratumoral. Las tasas de supervivencia general a los 5 años y de supervivencia libre de recaídas después de la colectomía, difirieron significativamente entre los grupos con índice de estroma tumoral o heterogeneidad del estroma intratumoral altos y bajos. El análisis multivariante identificó una proporción de estroma tumoral baja (cociente de riesgos instantáneos: 1.90, p = 0.03) y una heterogeneidad estromal intratumoral alta (cociente de riesgos instantáneos: 2.44, p = 0.002) como factores independientes de mal pronóstico para la supervivencia libre de recaídas. La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral se correlacionaron con la duración de la recurrencia desde la cirugía.Además, la recurrencia posoperatoria dentro de los 2 años se predijo con mayor precisión mediante el uso del índice de estroma tumoral o la heterogeneidad del estroma intratumoral que mediante el uso del estadio patológico. En una cohorte de validación, la concordancia interobservador fue evaluada por dos observadores, y el coeficiente Kappa de Cohen para la proporción de estroma tumoral y la heterogeneidad estromal intratumoral reveló una concordancia interobservador sustancial (valor Kappa: 0.70, 0.60, respectivamente).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo de una sola institución.CONCLUSIONES:La proporción del estroma tumoral y la heterogeneidad del estroma intratumoral calculadas mediante software de análisis de imágenes tienen potencial como biomarcadores de imagen para predecir la supervivencia de los pacientes con cáncer de colon tras la colectomía. Consulte Video Resumen en http://links.lww.com/DCR/C114 . (Traducción-Dr. Osvaldo Gauto ).

Survival Outcomes after Elective or Emergency Surgery for Synchronous Stage IV Colorectal Cancer.

Patients with stage IV colorectal cancer (CRC) who have not undergone primary tumor resection (PTR) are at risk of sudden medical emergencies. Despite the ongoing controversy over the necessity and timing of PTR in patients with stage IV CRC, studies comparing the survival outcomes of elective and emergency surgery in this population are scarce. This is a retrospective study conducted at a single institute. The patients were divided into two groups: the elective surgery (ELS) group (n = 46) and the emergency surgery (EMS) group (n = 26). The primary outcome was 2-year overall survival (OS). During a median follow-up period of 27.0 months, the 2-year OS was significantly better in the ELS group (80% vs. 42.9%, p = 0.002). No significant differences were observed in the 2-year relapse-free survival and 30-day postoperative complication rates. Planning and performing elective surgery could help increase the survival rate of patients with synchronous stage IV CRC, especially those that undergo simultaneous or staged metastasectomy.

Prognostic risk factors for pT4 colon cancer: A retrospective cohort study.

The present study aimed to clarify the prognostic risk factors for pathological T4 (pT4) colon cancer and provide a basis for improved treatment in affected patients. The current retrospective cohort study included 83 consecutively enrolled patients who underwent curative surgery for primary pT4 colon cancer between January 2014 and December 2021 at Tokyo Medical Women's University (Tokyo, Japan). Oncological outcomes, including recurrence pattern, were compared between patients with pT4a and pT4b colon cancer. Independent risk factors associated with overall survival (OS) and relapse-free survival (RFS) were analyzed using a multivariate Cox regression model. The 3-year OS rates were 85.1 and 95.0% in the pT4a and pT4b groups (P=0.089) and 3-year RFS rates were 64.1 and 60.5% (P=0.589), respectively. Moreover, the 3-year peritoneal recurrence-free survival was 71.0 and 90.2% (P=0.085) in these groups, respectively. Independent risk factors for OS were histology (mucinous or poorly differentiated adenocarcinoma), tumor location (right-sided) and pN status (positive). The risk factors for RFS were histology and pN status. Patients with pT4b colon cancer and R0 resection may not have a poorer prognosis compared with those with pT4a colon cancer. However, patients with pT4a colon cancer tended to have more peritoneal recurrence patterns. Histology and pN status were associated with OS and RFS, and right-sided colon cancer was also a risk factor for OS.

Transanal down-to-up dissection of the distal rectum as a viable approach to achieve total mesorectal excision in laparoscopic sphincter-preserving surgery for rectal cancer near the anus: a study of short- and long-term outcomes of 123 consecutive patients from a single Japanese institution

BackgroundIn rectal cancer (RC) surgery, the complexity of total mesorectal excision (TME) in laparoscopic sphincter-preserving surgery (lap-SPS) for RC near the anus has been a critical issue. Recently, technical assistance via the anus for complete TME has been receiving attention. This study aimed at clarifying the transanal down-to-up dissection viability for achieving TME in lap-SPS for RC near the anus.MethodsWe evaluated surgical and oncological outcomes of a total of 123 consecutive patients undergoing either a transanal rectal dissection (TARD) under direct vision mobilizing the most difficult portion of TME via the anus or the transanal TME by using an endoscopic system (TaTME) for achieving TME in lap-SPS for RC near the anus between January 2006 and February 2021.ResultsA total of 123 consecutive patients (83 men) with a median age of 66 years (range 33–86 years) were included. TARD and TaTME were performed for 50 (40.7%) and for 73 (59.3%) patients, respectively. Preoperative treatment was performed for 40 (32.5%) patients, resulting in a complete pathological response in 5 (12.5%) patients. Intersphincteric resection was performed significantly more in the TARD group (p<0.001). Although the TaTME group needed a longer operative time at the transanal portion (p<0.001), the median blood loss was lower (p<0.001). Postoperative complications with the Clavien–Dindo classification grade ≧2 developed in 52 (42.3%) patients. Urinary dysfunction and stoma-related complications were found most frequently. More patients needing medication for urinary dysfunction were found in the TARD group, but a significant difference was not observed (10.0% vs. 6.8%, p=0.526). The quality of TME was good for almost all patients. Recurrence developed in 18 (14.6%) patients. The 5-year overall survival (OS) and relapse-free survival (RFS) rates in 123 patients were 95.8% and 88.8%, respectively. The 5-year OS and RFS between the two groups were comparable.ConclusionsOur data suggested that a transanal down-to-up dissection of the distal rectum might be a viable approach in lap-SPS for RC near the anus. Further studies are needed to examine the differences between TARD and TaTME.

Frontline Combination of Hyper-CVAD with Ponatinib for Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia-6-Year Follow-up Results

Background: The combination of cytotoxic chemotherapy with a BCR::ABL1 tyrosine kinase inhibitor (TKI) has historically been standard of care for patients (pts) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib is 3rd generation TKI with more potent BCR::ABL1 inhibition than earlier-generation TKIs. Ponatinib also suppresses T315I clones, which are responsible for most relapses with other TKIs. Here we present the 6-year follow-up results of hyper-CVAD plus ponatinib for patients with newly diagnosed Ph+ ALL. Methods: This was a phase 2, single-arm study to evaluate the efficacy and safety of hyper-CVAD with ponatinib in adults with newly diagnosed Ph+ ALL. Pts age 18 years or older with previously untreated Ph+ ALL were eligible; pts who had received 1 to 2 courses of prior chemotherapy, with or without a TKI, were also eligible. Pts were required to have an ECOG performance status of 2 or less, bilirubin <3mg/dl, creatinine <3mg/dl, and normal cardiac function. Pts received hyper-CVAD alternating with high-dose methotrexate and cytarabine for 8 cycles. Initially, ponatinib was given at a dose of 45 mg daily. Due to 2 deaths due to cardiovascular events related to ponatinib, beginning with pt #37, the protocol was amended. After the amendment, ponatinib was administered at a dose of 45 mg for 14 days in cycle 1, then 30mg daily once patients achieved CR and 15mg daily once a complete molecular response (CMR) was achieved. Maintenance therapy was given for 2 years, vincristine, prednisone and ponatinib. Pts received 12 doses of intrathecal chemotherapy with alternating doses of cytarabine and methotrexate. Results: 86 pts were treated. Pts characteristics are summarized in Table 1. The median age was 46 years (range 21-80). Sixty-six pts (77%) had received no prior ALL-directed therapy, and 20 pts (23%) had received 1-2 courses of therapy prior to enrollment. Among these 20 pts, 18 were in CR and 2 had persistent disease at the time of enrollment. Sixty three pts (73%) had a p190 transcript, and 21 (24%) had a p210 transcript. Among 68 pts with active disease at enrollment, all pts achieved CR. Among 54 pts evaluable for cytogenetic response, all pts achieved complete cytogenetic response, including 50 pts (93%) after 1 cycle. Among 85 pts evaluable for molecular response, 83 pts (98%) achieved at least a major molecular response and 73 pts (86%) achieved a CMR. No pts died in the first 4 weeks of therapy. After a median follow up of 75 months (range, 16-123+ months), the 5-year overall survival (OS) and relapse-free survival rates were 75% and 68%, respectively (Figure 1). Twenty pts (23%) underwent stem cell transplantation (SCT) in first remission (5 of whom relapsed post SCT and 1 of whom died from post-SCT complications), 10 pts (12%) died in CR, 13 pts (19%) relapsed without SCT, and 43 pts (50%) are in ongoing remission without SCT. Of the relapsed pts, 5 were on ponatinib at the time of relapse, 2 of whom acquired an E255K kinase domain mutation at relapse; and 5 were on imatinib or dasatinib at the time of relapse, 3 of whom acquired a T315I kinase domain mutation. Among the 10 deaths in CR, 2 were treatment-related (both due to myocardial infarction before the amendment to implement lower doses of ponatinib). In a 8-month landmark analysis, the 5-year OS for pts without ASCT and with ASCT were 87% and 70%, respectively (p =0.09). Among the pts who are in ongoing remission without ASCT, 3 received subsequent therapy for MRD-positive disease. The most common grade ≥3 AE was infections and/or febrile neutropenia, seen in 82 pts (95%). Other grade ≥3 AEs including elevated transaminases in 25 pts (29%), increased amylase and/or lipase in 15 (17%), hyperbilirubinemia in 13 pts (15%), and clinical pancreatitis in 13 pts (15%). Five pts (6%) had a grade ≥3 venous thrombotic event, and 5 pts (6%) had a grade ≥3 arterial cardiovascular event. Two patients died from ponatinib-related cardiovascular complications, both from MI during cycle 2. Conclusion: The combination of hyper-CVAD and ponatinib results deep and durable remissions in pts with newly diagnosed Ph+ ALL. The overall CMR rate was 86% and the 5-year OS was 75%, which compares favorably with regimens using first- or second-generation TKIs in this population. The combination was safe; the use of lower doses of ponatinib maintained efficacy and mitigated the risk of ponatinib-related toxicity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic differences between oligometastatic and polymetastatic disease after resection in patients with colorectal cancer and hepatic or lung metastases: Retrospective analysis of a large cohort at a single institution

BackgroundLong-term survival data are lacking, and prognostic factors are not well-defined for patients with colorectal cancer and hepatic or lung metastases. This study evaluated the outcomes after resection of oligometastatic hepatic or lung metastases from colorectal cancer and sought to identify prognostic factors. MethodsWe retrospectively investigated 1,123 patients with colorectal cancer and hepatic or pulmonary metastases who underwent curative surgery between January 1991 and December 2016. ResultsOf the 1,123 patients, 719 had hepatic metastases, 287 had pulmonary metastases, and 117 had both. The 5-year overall survival rate was 52.3% in the hepatic metastases group, 70.4% in the pulmonary metastases group, and 71.4% in the hepatic and pulmonary metastases group (P < .001). In total, 1,045 patients had oligometastases (1–5 metastatic lesions in 1 or 2 organs) and 78 had polymetastases (≥6 metastases in 1 or 2 organs). Prognosis was significantly better in patients with oligometastases than in those with polymetastases. The 5-year overall survival rate was 59.0% in the oligometastases group and 35.3% in the polymetastases group (P < .001); the respective 5-year relapse-free survival rates were 37.5% and 11.6% (P < .001). Multivariable analysis identified predictors of both poor overall survival and relapse-free survival to be a high carcinoembryonic antigen level before the first metastasectomy, largest metastasis measuring ≥2 cm, polymetastases, and synchronous metastases. ConclusionPrognosis after curative resection was better in patients with oligometastatic colorectal cancer in the liver or lung than in those with polymetastases. Multidisciplinary decision-making strategies, including about surgery, should be based on number of metastases rather than their site.

Neck level Ib-sparing versus level Ib-irradiation in intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma with high-risk factors: A propensity score-matched cohort study

AimLevel Ib lymph nodes metastasis is rare in nasopharyngeal carcinoma (NPC). We aimed to evaluate the feasibility of sparing level Ib-irradiation in NPC patients with high-risk factors. Materials and methodsFour hundred forty-three NPC patients with radiologic extranodal extension (rENE) or level II lymph node maximal axial diameter (MAD) ≥ 20 mm treated by intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were included in this study. Propensity score matching (PSM) was applied to balance potential prognostic factors (including age, sex, T and N stage, pretreatment EBV DNA level, and level II rENE and MAD) between patients who received and omitted level Ib irradiation. Kaplan–Meier analysis and the log-rank test were used to compare regional survival outcomes. ResultsPSM resulted in 169 matched pairs of eligible patients. The median follow-up period was 119 months in the matched cohort. The number of level Ib failure in the level Ib-sparing and level-Ib irradiation groups were 3/169 (1.8 %) vs 2/169 (1.2 %), P > 0.999. And the 5-year regional relapse-free survival (RRFS) rates of the two groups were 88.4 % vs 92.6 %, respectively. After PSM, RRFS (hazard ratio [HR]: 1.508, 95 % confidence interval [CI]: 0.762–2.986, P = 0.239), OS (HR: 1.219, 95 % CI: 0.754–1.972, P = 0.418), distant metastasis-free survival (DMFS) (HR: 1.605, 95 % CI: 0.900–2.863, P = 0.109), and local relapse-free (LRFS) (HR: 0.956, 95 % CI: 0.436–2.095, P = 0.910) were similar in the two arms. The incidence of grade ≥ 1 dry mouth after 5 years was higher in the level Ib-irradiation group (27.5 % vs 16.5 %, P = 0.029). However, the incidences of grade 3–4 late toxicities were similar between the two groups. ConclusionNeck level Ib-sparing appears to be safe and feasible in NPC patients with rENE or level II MAD ≥ 20 mm and negative level Ib lymph nodes. Compared with cervical level Ib-irradiation, omission of irradiation to level Ib provides less dry mouth symptom.

Timing of additional neoadjuvant chemotherapy in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and total mesorectal excision

BackgroundIn locally advanced rectal cancer (LARC), the optimal sequence of neoadjuvant chemotherapy in relation to neoadjuvant chemoradiotherapy and before total mesorectal excision is unknown.MethodsA total of 426 LARC patients, treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision, between January 2010 and December 2018, were studied retrospectively. Patients were divided into induction and consolidation chemotherapy groups. Overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates for the 2 groups were compared. Multivariate analysis hazard ratios (HR) with 95% confidence intervals (CI) to identify survival predictors.ResultsMedian follow-up was 37 (range, 7–162) months. The 3-year overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates were 93.8%, 71.6%, 93.5%, and 74.4%, respectively. For those receiving either induction or consolidation chemotherapy, 3-year disease-free survival rates were 82.5% and 67.7%, respectively (P = 0.021), distant metastasis-free rates were 85.4% and 70.8%, respectively (P = 0.024), and both overall and locoregional relapse-free survival rates did not differ significantly. Absence of neural invasion was an independent predictor of disease-free (HR = 0.49, 95% CI 0.25–0.97, P = 0.04) and distant metastasis-free (HR = 0.49, 95% CI 0.25–0.98, P = 0.04) survival. Both ypTN stage III (vs.0-II) and consolidation (vs. induction) chemotherapy were independent predictors of disease relapse (HR = 1.95, 95% CI 1.47–2.58, P < 0.001; HR = 1.68, 95% CI 1.01–2.79, P = 0.046; respectively) and distant metastasis (HR = 2.04, 95% CI 1.51–2.76, P < 0.001; HR = 1.75, 95% CI 1.03–2.99, P = 0.04; respectively).ConclusionsLARC patients receiving neoadjuvant chemoradiotherapy and total mesorectal excision had better disease-free and distant metastasis-free survival, with induction rather than consolidation neoadjuvant chemotherapy.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Simple SummaryMerkel cell carcinoma is a very rare and highly aggressive neuroendocrine carcinoma originating from the skin. Exceptionally it presents with a nodal localization without a cutaneous primary site and distant metastases. This entity is controversial in terms of origin and clinical management. The main histological differential diagnosis is that of small cell neuroendocrine carcinoma. As a referral center for neuroendocrine neoplasms with more than 20 years of experience we have dealt with patients showing this clinical context several times and we usually manage them within our dedicated multidisciplinary team. Due to the extreme rarity of the entity and undefined clinical management, we report our single-center series and detail some of the diagnostic and therapeutic aspects. Our analysis can be helpful for centers which manage these patients and future investigations on the topic.Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0–68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8–79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5–95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0–97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data.

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy. Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab. 18F-FDG PET/CT scans were performed before R-CHOP for initial staging. The largest diameter of tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment 18F-FDG PET/CT scans. Receiver-operating characteristic curves analysis was introduced for assessing the optimal criteria. Kaplan-Meier curve survival analysis was performed to evaluate both relapse free survival (RFS) and overall survival (OS). A total of 15 patients (12 males and 3 females) with a mean age of 56 (range, 30-73) years were enrolled. The median follow-up period of these patients was 73 months (range, 11-108 months). Four (27%) patients relapsed. Of them, three died during follow-up. Median values of the largest tumor size, highest SUVmax, MTV, and TLG were 5.3 cm (range, 2.0-16.4 cm), 20.2 (range, 11.1-67.4), 231.51 (range, 15-38.34), and 1277.95 (range, 238.37-10341.04), respectively. Patients with SUVmax less than or equal to 16.9 showed significantly worse RFS than patients with SUVmax greater than 16.9 (5-year RFS rate: 60% vs. 100%, p = 0.008). Patients with SUVmax less than or equal to 16.9 showed significantly worse OS than patients with SUVmax greater than 16.9 (5-year OS rate: 80% vs. 100% p = 0.042). Higher SUVmax at pretreatment 18F-FDG PET/CT was associated with better relapse free survival and overall survival in DLBCL patients after consolidation therapy with 131I-rituximab. However, because this study has a small number of patients, a phase 3 study with a larger number of patients is needed for clinical application in the future.

313. RISK FACTORS FOR RECURRENCE IN ADVANCED ESOPHAGEAL CANCER PATIENTS WHO RECEIVED NEOADJUVANT CHEMOTHERAPY FOLLOWED BY ESOPHAGECTOMY

Abstract Recently, nivolumab adjuvant therapy has become a new treatment option in Japan. However, who is the good candidate of this adjuvant therapy has not been fully investigated. The aim of this study was to clarify the risk factors for recurrence in advanced esophageal cancer patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy. We retrospectively reviewed the records of 83 patients with advanced thoracic esophageal cancer who received NAC followed by esophagectomy between 2000 and 2018 (69 men and 14 women with a median age of 65 years). We evaluated relapse-free survival (RFS) and investigated the risk factors for recurrence by multivariate analysis. The regimen of NAC was Cisplatin +5-FU (CF) in 74 patients, Docetaxel + Cisplatin +5-FU in six, and CF with radiotherapy in three. The median follow-up period after esophagectomy was 53 months. The 3-year RFS rate was 58.8%. Multivariate analyses revealed ypT3–4 (Hazard ratio, 3.71; 95% confidence interval, 1.67–8.29), lymphatic invasion (3.45; 1.62–7.39), and postoperative infectious complications (2.99; 1.47–6.07) were significant risk factors for recurrence. Moreover, the prognosis of the patient group with 2 or more risk factors was significantly worse than that of the patient group with 0–1 factor (The 3-year RFS rates, 75.2% vs. 23.1%; p &amp;lt; 0.001). ypT3–4, lymphatic invasion, and postoperative infectious complications were significant risk factors for recurrence after esophagectomy after neoadjuvant chemotherapy. The prognosis of the patient group with 2 or more these risk factors was significantly worse, therefore, it is considered to be a candidate for nivolumab adjuvant therapy.

Clinical features and outcomes of fusion gene defined adult Ph-negative B-cell precursor acute lymphoblastic leukemia patients: A single institutional report.

More clinical studies are needed to clarify the risk stratification by the integration of all fusion genes in adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A total of 320 consecutive adult Ph-negative BCP-ALL patients who had been tested classical fusions (KMT2A rearrangement and TCF3-PBX1) at diagnosis were further retrospectively screened novel fusion genes (Ph-like, ZNF384 and MEF2D fusions) by multiplex real-time quantitative PCR (RQ-PCR). Classical fusions were identified in 12.5% of patients, while 4.4%, 17.2% and 3.8% of patients were identified Ph-like, ZNF384 and MEF2D fusions, respectively. 1-course CR rate, relapse-free survival (RFS) and overall survival (OS) rates tended to show or showed statistically significant differences among fusion-defined subgroups (P = 0.084, 0.001 and 0.0093, respectively). Based on individual outcomes, patients with KMT2A rearrangement, TCF3-PBX1, Ph-like, and MEF2D fusions were classified into fusion-defined high-risk group (n = 66, 20.6%). High-risk group had significantly lower 3-year RFS and 3-year OS rates than standard-risk group (P 0.001 and = 0.0022), and was an independent adverse prognostic factor for RFS in the entire cohort (P 0.001). In conclusion, the spectrum of fusion genes in the current Chinese cohort was distinct from that in reports from western countries. Detection of fusion genes improved risk stratification in adult Ph-negative BCP-ALL patients.

Prognostic factors for relapse-free survival in stage IB-IIIA primary lung adenocarcinoma by epidermal growth factor receptor mutation status

BackgroundPathological stage IB-IIIA lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation (Mt) has a high recurrence rate even after complete resection. However, there have been few reports on the risk factors for Mt recurrence. This study aimed to analyze the clinicopathological factors related to the relapse-free survival (RFS) of patients with pathological stage IB-IIIA primary lung adenocarcinoma with and without an EGFR mutation.MethodsPatients who underwent curative surgery for Mt (n = 208) harboring the EGFR exon 21 L858R point mutation or EGFR exon 19 deletion mutation and EGFR mutation wild-type lung adenocarcinoma (Wt, n = 358) between January 2010 and December 2020 were included. Patients who received adjuvant EGFR-tyrosine kinase inhibitors were excluded. The prognostic factors for RFS were analyzed using a multivariable Cox regression analysis.ResultsThe 5-year RFS rates in the Mt and Wt groups were 43.5 and 52.3%, respectively (p = 0.907). Prognostic factors for RFS in the Mt group included smoking history (hazard ratio [HR], 1.49; p = 0.049), blood vessel invasion (HR, 1.84; p = 0.023), and lymph node metastasis (HR, 1.96; p = 0.005). However, adjuvant chemotherapy was not a prognostic factor (HR, 1.02; p = 0.906). In contrast, positron emission tomography (PET) max standardized uptake value (SUV) ≥ 6.0 (HR, 1.53; p = 0.042), lymphatic vessel invasion (HR, 1.54; p = 0.036), lymph node metastasis (HR, 1.79; p = 0.002), and adjuvant chemotherapy (HR, 0.60; p = 0.008) were prognostic factors for RFS in the Wt group.ConclusionsPrognostic factors for RFS in stage IB-IIIA primary lung adenocarcinoma differ by epidermal growth factor receptor mutation status. The impact of adjuvant chemotherapy on RFS also differed by EGFR mutation status.

Spatial analysis and CD25-expression identify regulatory T cells as predictors of a poor prognosis in colorectal cancer

AbstractRegulatory T cells (Tregs) are a heterogeneous cell population that can either suppress or stimulate immune responses. Tumor-infiltrating Tregs are associated with an adverse outcome from most cancer types, but have generally been found to be associated with a good prognosis in colorectal cancer (CRC). We investigated the prognostic heterogeneity of Tregs in CRC by co-expression patterns and spatial analyses with diverse T cell markers, using multiplex fluorescence immunohistochemistry and digital image analysis in two consecutive series of primary CRCs (total n = 1720). Treg infiltration in tumors, scored as FOXP3+ or CD4+/CD25+/FOXP3+ (triple-positive) cells, was strongly correlated to the overall amount of CD3+ and CD8+ T cells, and consequently associated with a favorable 5-year relapse-free survival rate among patients with stage I–III CRC who underwent complete tumor resection. However, high relative expression of the activation marker CD25 in triple-positive Tregs was independently associated with an adverse outcome in a multivariable model incorporating clinicopathological and known molecular prognostic markers (hazard ratio = 1.35, p = 0.028). Furthermore, spatial marker analysis based on Voronoi diagrams and permutation testing of cellular neighborhoods revealed a statistically significant proximity between Tregs and CD8+-cells in 18% of patients, and this was independently associated with a poor survival (multivariable hazard ratio = 1.36, p = 0.017). These results show prognostic heterogeneity of different Treg populations in primary CRC, and highlight the importance of multi-marker and spatial analyses for accurate immunophenotyping of tumors in relation to patient outcome.

Analysis of treatment results and survival rates with assessment of prognostic factors in locally advanced well-differentiated thyroid cancer

Objective. To analyze the results of treatment and prognostic factors of general and relapse-free survival in patients with locally advanced welldifferentiated thyroid cancer who received surgical treatment, radiation therapy, radioiodine therapy and chemotherapy. Methods. T he retrospective study included patients with a verified diagnosis of locally advanced well-differentiated thyroid cancer who received treatment at the National Medical Research Centre of Oncology n. a. N. N. Petrov (Saint Petersburg, Russia). The study endpoints were overall and disease-free survival. Results. Seventy-six patients were included in the study. The average age of patients was 60.0 (20.3) years, the median age was 62.0 (52.8–73.0) years. 25 (32.9 %) of 76 patients were male. The median overall survival was 109.0 months, and the 5-year overall survival rate was 80 months (95 % CI: 65.6–97.5). The median relapse-free survival was 108.6 months (the lower limit was 95 % CI was 56.7), and the 5-year relapse-free survival rate was 62.1 months (95 % CI: 46.5–83.0). Conclusion. Analysis of risk factors revealed a statistically significant relationship between tumor invasion into the larynx and chemotherapy. Factors such as the patient’s age and neck lymph node surgery are associated with the risk of recurrence or death.

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study.

Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p=0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer

The long-term safety of laparoscopic distal gastrectomy for locally advanced gastric cancer (AGC) remains uncertain given the lack of 5-year follow-up results. To compare the 5-year follow-up results in patients with clinically AGC enrolled in the Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-02 randomized clinical trial who underwent laparoscopic or open distal gastrectomy. The KLASS-02, a multicenter randomized clinical trial, showed that laparoscopic surgery was noninferior to open surgery for patients with locally AGC. The present study assessed the 5-year follow-up results, including 5-year overall survival (OS) and relapse-free survival (RFS) rates and long-term complications, in patients enrolled in KLASS-02. From November 21, 2011, to April 29, 2015, patients aged 20 to 80 years diagnosed preoperatively with locally AGC were enrolled. Final follow-up was on June 15, 2021. Data were analyzed June 24 to September 9, 2021. Patients were treated with R0 resection either by laparoscopic gastrectomy or open gastrectomy as the full analysis set of the KLASS-02 trial. Five-year OS and RFS rates, recurrence patterns, and long-term surgical complications were evaluated. This study enrolled a total of 1050 patients. A total of 974 patients were treated with R0 resection; 492 (50.5%) in the laparoscopic gastrectomy group (mean [SD] age, 59.8 [11.0] years; 351 men [71.3%]) and 482 (49.5%) in the open gastrectomy group (mean [SD] age, 59.4 [11.5] years; 335 men [69.5%]). In patients who underwent laparoscopic and open distal gastrectomy, the 5-year OS (88.9% vs 88.7%) and RFS (79.5% vs 81.1%) rates did not differ significantly. The most common types of recurrence were peritoneal carcinomatosis (73 of 173 [42.1%]), hematogenous metastases (36 of 173 [20.8%]), and locoregional recurrence (23 of 173 [13.2%]), with no between-group differences in types of recurrence at each cancer stage. The correlation between 3-year RFS and 5-year OS at the individual level was highest in patients with stage III gastric cancer (ρ = 0.720). The late complication rate was significantly lower in the laparoscopic than in the open surgery group (32 of 492 [6.5%] vs 53 of 482 [11.0%]). The most common type of complication in both groups was intestinal obstruction (13 of 492 [2.6%] vs 24 of 482 [5.0%]). The 5-year outcomes of the KLASS-02 trial support the 3-year results, which is the noninferiority of laparoscopic surgery compared with open gastrectomy for locally AGC. The laparoscopic approach can be recommended in patients with locally AGC to achieve the benefit of low incidence of late complications. ClinicalTrials.gov Identifier: NCT01456598.