Relapse-free Survival Rates Research Articles

The impact of delayed adjuvant chemotherapy on survival in gastric cancer patients with and without preoperative chemotherapy

AbstractAimAdjuvant chemotherapy (AC) is the standard treatment for patients with advanced gastric cancer (GC), yet the optimal timing for its initiation remains unclear. Besides, no studies have definitively established when AC should begin in patients receiving preoperative chemotherapy (PC). This study aimed to determine the optimal timing for initiating AC in patients with GC who underwent curative gastrectomy, either with or without PC.MethodsA total of 446 patients who underwent curative gastrectomy were evaluated, including 140 who received AC: 72 without PC and 68 with PC. Patients were categorized into two groups based on when they began AC: the early initiation group (within 8 weeks post‐surgery), and the late initiation group (8 weeks or later post‐surgery).ResultsIn the non‐PC cohort, the 3‐year relapse‐free survival (RFS) rates were 71% in the early group versus 56% in the late group (p = 0.49), while the 3‐year overall survival (OS) rates were 94% versus 73% (p = 0.003). Similar trends were observed in the PC cohort; the 3‐year RFS rates were 59% versus 19% (p = 0.002), and the 3‐year OS rates were 69% versus 48% (p = 0.02). Multivariate analysis identified pretherapeutic distant metastasis (p < 0.001) and delayed AC initiation (≥8 weeks) (p = 0.001) as independent predictors of worse prognosis.ConclusionDelayed initiation of AC is associated with significantly poorer postoperative survival in patients with GC, irrespective of whether PC was administered. These findings emphasize the importance of timely AC initiation to improve long‐term outcomes in this patient population.

Efficacy and tolerability of neoadjuvant therapy with Talimogene laherparepvec in cutaneous basal cell carcinoma: a phase II trial (NeoBCC trial).

We present a single-arm, phase II, neoadjuvant trial with the oncolytic virus talimogene laherparepvec (T-VEC) in 18 patients with difficult-to-resect cutaneous basal cell carcinomas. The primary end point, defined as the proportion of patients, who after six cycles of T-VEC (13 weeks), become resectable without the need for plastic reconstructive surgery, was already achieved after stage I (9 of 18 patients; 50.0%); thus the study was discontinued for early success. The objective response rate was 55.6% and the complete pathological response rate was 33.3%. Secondary end points included safety, relapse-free survival and overall survival, time to occurrence of new basal cell carcinomas and biological read outs. Only mild adverse events occurred. The 6-month relapse-free survival and overall survival rates were 100%. In two patients a new basal cell carcinoma was diagnosed. T-VEC led to a significant increase in cytotoxic T cells (P = 0.0092), B cells (P = 0.0004) and myeloid cells (P = 0.0042) and a decrease in regulatory T cells (P = 0.0290) within the tumor microenvironment. Together, neoadjuvant T-VEC represents a viable treatment option for patients with difficult-to-resect basal cell carcinomas (EudraCT no. 2018-002165-19).

Post-transplant cyclophosphamide plus anti-thymocyte globulin decreased serum IL-6 levels when compared with post-transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation

BackgroundPost-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.MethodThe clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023.ResultsForty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).ConclusionSerum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis.

This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78Gy. The median follow-up period was 82months (range: 32-140months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.

Female Oncofertility and Immune Checkpoint Blockade in Melanoma: Where Are We Today?

The incidence of melanoma among young adults has risen, yet mortality has declined annually since the introduction of immune checkpoint inhibitors (ICI). The utilization of peri-operative ICI has significantly altered the treatment landscape in melanoma, with PD-1 inhibitors showing promising efficacy in improving relapse-free survival rates in high-risk stage II-III disease. With the increasing use of ICI, secondary concerns have emerged regarding the impact of cancer drugs on fertility and reproductive health among women of childbearing potential, especially in early-stage cancer settings. The exclusion of pregnant women from trials contributes to limited human data and clinical uncertainties, such as maternal and fetal toxicities related to ICI exposure during pregnancy, as well as the value of fertility preservation before ICI therapy. Uncertainty persists regarding pregnancy post-adjuvant immunotherapy, given the potential detrimental effects of hormonal and immunological changes during pregnancy on melanoma relapse. There is additional uncertainty about whether pregnancy-associated melanoma (PAM) represents a distinct disease entity that warrants tailored management compared to non-pregnant cases. Our review aims to give an overview of oncofertility practices among female melanoma patients after immunotherapy. We also focus on the literature gap in the published evidence and synthesize summaries regarding ICI toxicities on reproductive health and fetal development, pregnancy planning, and recurrence risks after melanoma treatment.

Experience of using chemotherapy treatment for the first recurrence of ovarian cancer

Background. The main goal of treating patients with recurrent ovarian cancer is to prolong life and improve its quality. Approaches to the treatment of recurrent ovarian cancer have changed over the past decade. The choice of antitumor drug therapy is determined by the duration of platinum-free interval and the use of targeted therapy with bevacizumab or olaparib. Treatment regimens for relapses are not unified and treatment outcomes are contradictory. Aim: to analyze treatment outcomes of different chemotherapy regimens in patients with the first recurrence of ovarian cancer, depending on the duration of platinum-free interval. Material and Methods. A retrospective analysis of the first recurrence of ovarian cancer in 446 patients treated at the Primorsky Regional Oncology Center in the period 2004–2021 was carried out. All patients were divided into two groups depending on the treatment option for relapse: repeated cytoreduction followed by chemotherapy or only second-line chemotherapy, and into four groups depending on the chemotherapy regimens: 1 – platinum and taxane agents; 2 – platinum and taxane agents with bevacizumab; 3 – platinum agents and non-taxane agents with bevacizumab; 4 – monotherapy with non-platinum agents with bevacizumab. Results. Significant advantages in progression-free survival after second-line chemotherapy (PFS-2) were observed in patients with platinum-resistant relapse after the 4th chemotherapy regimen. Patients with platinum-sensitive relapse had the best treatment outcomes after the 3rd chemotherapy regimen and repeated cytoreduction followed by chemotherapy with a platinum-free interval of 6–12 months and 12–24 months with any platinum-containing chemotherapy regimen. In the platinum-free interval of more than 24 months, significant benefits were observed with a combination of platinum and taxane agents + bevacizumab. In the group of patients without surgery, there were significant benefits in all three intervals when prescribing a combination of platinum and non-oxane agents ± bevacizumab. There was a tendency to increase PFS-2 in patients with low-grade serous ovarian carcinoma compared with patients with high-grade serous carcinoma. The best rates of relapse-free survival were noted with maintenance therapy with olaparib. Conclusion. In patients with localized recurrence of ovarian cancer and a platinum-free interval of more than 6 months, it is advisable to perform repeated cytoreduction followed by chemotherapy, taking into account the duration of the platinum-free interval. The administration of PARP inhibitors in the maintenance therapy of platinum-sensitive recurrence of ovarian cancer improves treatment results.

Experience in performing multivisceral resections for pelvic cancer

Background. Treatment of patients with locally advanced pelvic cancer remains challenging. The use of modern surgical techniques has expanded the feasibilities of performing multivisceral resections (MVR) in this category of patients. However, the postoperative period in patients who have undergone MVR is associated with a high risk of developing postoperative complications. The purpose of the study was to assess the short-term and long-term treatment outcomes in patients with locally advanced and multiple-primary pelvic cancer. Material and Methods. From 2009 to 2021, 114 patients treated in the clinics of Cancer Research Institute of Tomsk National Research Medical Center underwent MVR for primary or recurrent rectal cancer (n=40, 35.1 % and n=4, 3.5 %, respectively), female reproductive cancer (endometrial cancer: n=18, 17.1 % and recurrent ovarian cancer: n=18, 17.1 %), primary and recurrent bladder cancer (n=15, 13.2 % and n=2, 1.8 %, respectively), synchronous multiple primary pelvic tumors (n=8, 7.0 %) and extraorgan mesenchymal tumors of the pelvis (n=4, 3.5 %). Paraneoplastic complications were observed in 31 (27.2 %) patients. Invasion to more than 2 adjacent pelvic organs was diagnosed in 52 (45.4 %) cases. Total pelvic evisceration (TPE) was performed in 9 (7.9 %) patients, including 5 (4.4 %) patients who underwent TPE for primary rectal cancer with extensive local spread and 4 (3.5 %) patients who underwent TPE for multiple primary cancer: 2 (1.75 %) for synchronous primary rectal cancer and bladder cancer and 2 (1.75 %) for primary rectal cancer and recurrent bladder cancer. MVR for rectal cancer was the most common (n=101, 88.6 %). Resections with the formation of colorectal anastomosis were performed in 75 (65.8 %) cases and obstructive resections of the rectum were performed in 14 (12.5 %) cases. Urinary tract surgeries were performed in 66 (57.5 %) cases. One-stage plastic surgery of the resected segment as a transposition of one or both ureters into the bottom of the bladder was performed in 22 (19.3 %) cases. Heterotopic and orthotopic plastic surgery of the bladder was performed in 19 (16.6 %) and 5 (4.4 %) cases, respectively. Combined uterine extirpations, including vaginal resection, were performed in 52 (45.4 %) cases. Grade III postoperative complications according to the Clavien–Dindo classification occurred in 18.4 % of cases. Urological complications were the most common (8.7 %). Postoperative mortality rate was 0.8 %. The assessment of the long-term outcomes was carried out using the example of patients with rectal cancer (n=45), as the most homogeneous and largest subgroup. The overall 3-year survival rate was 71.1 % and the relapse-free 3-year survival rate was 60.0 %. Conclusion. Treatment of locally advanced pelvic cancer requires extensive surgeries performed by a multidisciplinary team of surgeons. The immediate results can be assessed as satisfactory. In case of resection of the urinary tract as a component of MVR, regardless of the primary localization of the tumor, primary plastic surgery of the bladder and/or ureters is preferable. Long-term outcomes allow us to consider MVR as a method of choice in the treatment of this group of patients.

Prognostic Value of the Modified Cachexia Index in Colorectal Cancer Patients Undergoing Curative Surgery.

The cachexia index (CXI) has been reported to be a useful indicator for predicting the prognosis of cancer patients. However, CXI calculation requires skeletal muscle index (SMI) measurements, which involves an analysis of computed tomography images using an imaging software program, which makes the calculation process highly complex and time-consuming. Recently, the modified cachexia index (mCXI), calculated using the urea-to-creatinine ratio (UCR) instead of SMI, has been reported to be a useful marker that is easier to calculate than CXI. This study aimed to evaluate the correlation between mCXI and the prognosis of patients with colorectal cancer (CRC). A total of 291 patients who underwent curative surgery for stage I-III CRC were enrolled. mCXI was calculated as the serum albumin concentration/neutrophil-to-lymphocyte ratio (NLR)/UCR. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of the mCXI for predicting prognosis. The median mCXI was 0.089 (range=0.012-0.354). The ROC curve analysis revealed that the appropriate cut-off value for mCXI was 0.113. The low mCXI group had significantly shorter relapse-free and overall survival rates than the high mCXI group (p=0.030 and p=0.014, respectively). mCXI, which does not require an image analysis, may be closely associated with prognosis in patients undergoing curative surgery for CRC.

Reduced-intensity chemotherapy with tyrosine kinase inhibitor followed by allogeneic transplantation is effective in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity. The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI. The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates. When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.

Clinical features and prognostic nomogram for therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Therapy-related acute myeloid leukemia (t-AML), which develops after cytotoxic therapy, has a poorer prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure, its efficacy varies among patients. In this retrospective study, we analyzed 154 patients with t-AML who underwent hematopoietic stem cell transplantation (HSCT) at our institution to determine their clinical characteristics and develop a prognostic nomogram. The median ages at t-AML diagnosis prior disease diagnosis was 42 and 39 years, respectively. Multivariate analysis identified key prognostic indicators: leukocyte count at AML diagnosis ≥ 7 × 10ˆ9/L, genetic abnormalities before HSCT, platelet engraftment ≥ 28 days, age at prior disease ≥ 45 years, and relapse of prior disease. We developed a prognostic nomogram for LGPAR by categorizing patients into low, medium, and high-risk groups. The 3-year and 5-year overall survival (OS) rates for these groups were 92.6%, 84.4%, 14%, and 92.6%, 76.6%, and 7%, respectively. The 3-year and 5-year relapse-free survival (RFS) rates were 80%, 75.9%, 10.7% and 80%, 72.6%, and 10.7% for the respective risk groups. The 3-year and 5-year non-relapse mortality (NRM) rates were 0%, 5.6%, 63.3% and 0%, 9.3%, and 63.3% for these groups, respectively. This novel prognostic nomogram culminates in the development of a clinical decision-support tool for patients with t-AML undergoing allo-HSCT.

Real World Data in Stage III Melanoma in Latino Low Middle Income Country: Prognostic Factors and Outcomes.

Malignant melanoma is a heterogeneous disease, with varying outcomes depending on the patient's race and ethnicity. Advanced stages can be tackled by novel targeted therapies and immunotherapy. We aimed to investigate the real-world data in Latino-Hispanic patients diagnosed with Stage III melanoma residing in Peru, a region marked by limited resources and healthcare infrastructure. Patients diagnosed with Stage III melanoma at the Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru were included from the years 2010 to 2020. Cox regression analysis was used to assess prognostic factors. Four hundred twelve patients were included, the median age of diagnosis was 63 years, with a male predominance (55.6%). Most of the patients presented with a lesion in the lower extremities (77.4%), acral lentiginous melanoma (35.4%), and ulcerated tumors (72.3%). 64.1% were diagnosed with Stage IIIC, and 27.2% received interferon-alpha therapy. With a median follow-up of 36 months, the relapse-free survival and overall survival rates were 26% and 78% at 3 years follow-up, respectively. Prognostic factors of event-free survival (EFS) were greater age (HR = 1.015, 95% CI: 1.005-1.025), ulcerated lesions (HR = 1.855, 95% CI: 1.221-2.820), N category, and the administration of interferon therapy (HR = 0.680, 95% CI: 0.488-0.947). While worse overall survival (OS) was associated with greater ages (HR = 1.032, 95% CI: 1.011-1.053) and the presence of ulceration (HR = 2.992, 95% CI:1.142-7.835). Stage III melanoma in the Hispanic-Latino population from Peru has worse survival rates than other races and populations despite similar prognostic factors of worse EFS and OS. In resource-limited settings, reducing barriers to receiving healthcare and broadening access to contemporary immunotherapy and targeted therapy are crucial measures to improve outcomes in patients with advanced melanoma.

Glucocorticoid tapering pace in microscopic polyangiitis and granulomatosis with polyangiitis in Japanese real-world practice: A propensity score-matched retrospective cohort study from the J-CANVAS registry

Abstract Objective To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice. Methods We retrospectively examined the Japan Collaborative Registry of ANCA-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens. Relapse-free survival rates were compared after propensity score matching. Results Of 364 eligible patients, 113 (31.0%) received standard tapering and 251 slower tapering. After matching, 87 pairs no significant difference was observed in relapse-free survival (p=0.506). Regarding the reduced regimen, there were so few patients (14/364, 3.8%) that statistical analysis was not performed. Conclusions The glucocorticoid tapering for MPA and GPA in Japanese real-world practice was found to be generally slower than the standard regimen revealing a huge evidence-practice gap. Additionally, slower tapering did not improve relapse-free survival and might cause unnecessary glucocorticoid exposure.

Prognostic value of HER2 2+ expression in patients with TNBC receiving adjuvant capecitabine.

In triple-negative breast cancer (TNBC) patients receiving adjuvant capecitabine, the impact of HER2 expression on survival outcomes is unclear. Between June 2017 and December 2023, 112 patients with TNBC who received adjuvant capecitabine due to residual masses after neoadjuvant chemotherapy (NACT) in three hospitals were identified. HER2 is analyzed through immunohistochemistry (IHC) and/or in situ hybridization in the core biopsy and/or post-surgical histopathologies. Relapse-free survival (RFS) and overall survival (OS), according to HER2 expression (0, 1 + , 2 +) status, were calculated (Kaplan-Meier method). Seventy-eight (69.6%) patients had HER2 zero, 20 (17.9%) patients had HER2 + 1, and 14 (12.5%) patients had HER2 + 2/ISH- BC. The 5-year OS was 62.6%, and the 5-year RFS was 55.8%. HER2 2 + expression was associated with worse OS (27.5 vs. 84.5months; HR 4.82, 95% CI 2.15-10.80, p < 0.001) and worse RFS (11.90months vs. not reached; HR 4.30, 95% CI 2.06-8.99, p < 0.001) compared with HER2 0/1 + expression. The 5-year OS rates were 32.7% and 72.1%, and the 5-year RFS rates were 30.6% and 64.7% in the HER2 2 + and HER2 0/1 + groups, respectively. No statistically significant differences were detected in clinicopathologic features or pathologic responses to NACT according to the HER2 expression level. Despite the use of the adjuvant capecitabine in HER2 2 + TNBC patients, these poor results will pave the way for further investigations of anti-HER2 therapeutic agents in adjuvant treatment.

Prognosis and tumor microenvironment in pseudohypoxic pheochromocytoma/paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors that occur in the adrenal medulla and extra-adrenal tissues, respectively. The prognosis and tumor microenvironment (TME) of pseudohypoxic PPGL as a major entity have not been fully described. Based on the clinical database of 65 patients with PPGL, we assessed the morphological features as well as the immunohistochemistry of pseudohypoxia-related proteins (SDHB and CAIX) and TME-related immune cell markers. Furthermore, we compared the relapse-free survival (RFS) rates in localized patients between the pathological subgroups. Among 50 available specimens, 84% and 30% of the cases exhibited at least one morphological adverse feature including vascular/capsular invasion and a Ki-67 index > 3%, respectively. The SDHB and CAIX positivity rates were 81% and 51%. Concerning the immune cell markers, the CD163-positive cell numbers were higher in hypoxia-associated PPGL composed of SDHB-negative or CAIX-positive cases than in non-hypoxia PPGL (median 66 vs. 23/mm2). Concerning prognosis, RFS rates were significantly lower in cases with Ki-67 indices > 3% and SDHB-negativity than in those with Ki-67 indices ≤ 3% and SDHB-positivity (3-year rate: 64% vs. 100%, P < 0.001; 57% vs. 100%, P = 0.03). In contrast, RFS was comparable between CAIX-positive and CAIX-negative PPGL cases. Our analyses suggested that SDHB-deficient PPGL exhibited a higher incidence of relapse. Furthermore, M2 macrophage infiltration in TME might be crucial in pseudohypoxic PPGL pathogenesis.

Long-term outcomes of S-1 and oxaliplatin neoadjuvant chemotherapy with total mesorectal excision and lateral lymph node dissection for rectal cancer

PurposeChemoradiotherapy (CRT) for rectal cancer is limited by its harmful side effects and its insufficient benefit on lateral lymph node metastases. The purpose of this study was to evaluate the long-term outcomes of S-1 and oxaliplatin with total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiation for rectal cancer.MethodsThe inclusion criteria were patients with stage II or III rectal cancer located within 10 cm from the anal verge. Fifty-two patients who underwent neoadjuvant chemotherapy (NAC) followed by TME and LLND were evaluated. The primary endpoint was the 3-year local recurrence. The secondary endpoints were the 3-year rates of relapse-free survival and overall survival. Expected post-NAC and surgical outcomes were prospectively analyzed.ResultsThe overall recurrence rate was 15.4%, with eight patients developing distant recurrences. The local recurrence rate was 7.7% (n = 4). Among the 4 patients with local recurrence, 3 (5.8%) patients had central pelvis recurrence, and 1 (1.9%) patient had lateral pelvic recurrence. The 3-year survival rate was 98.1%, and the 3-year relapse-free survival rate was 84.6%. The risk factors for local recurrence were mucinous carcinoma (p = 0.016) and a positive resection margin (p = 0.009). Pathological mesorectal lymph node metastasis and local recurrence were independent risk factors for poor survival.ConclusionsAlthough preoperative chemotherapy and TME with LLND are sufficient to control local recurrence, some cases will require more aggressive chemotherapy with radiation therapy.

Toxicity profile and clinical outcomes of stereotactic body radiotherapy with afocal boost without fiducials or perirectal hydrogel spacer for localized prostate cancer.

Whole-prostate dose escalation in stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa) can improve oncological outcomes, albeit at the cost of increased toxicity. Afocal boost to the dominant intraprostatic lesion (DIL) is gaining interest as an alternative approach. Herein, we investigate the safety and efficacy of this approach. This retrospective study enrolled patients with localized PCa who underwent five-fraction SBRT with afocal boost to the DIL at our institution between May 2016 and August 2021. The prescription doses to the whole prostate were 35 and 36.25 Gy for low- to favorable intermediate-risk PCa and unfavorable intermediate- to high-risk PCa, respectively. The focal boost to the DIL was up to 115-140% of the prescribed dose. None of the patients underwent pretreatment fiducial or perirectal hydrogel spacer placement. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities and oncological outcomes were assessed. Among the 520 patients, 44% were categorized as patients with high-risk PCa. The median follow-up period was 42.9months. No acute or late grade ≥3 toxicities were observed. Acute and late grade2 GU toxicities were observed in 22.3 and 6.1%, respectively, while GI toxicities were observed in 2.1 and 0.8% of the patients. The 4‑year relapse-free survival rate was 94.8% among all patients. Our results indicate that SBRT with afocal boost without fiducials or perirectal hydrogel spacer for localized PCa has apromising toxicity profile and oncological outcomes. Longer follow-up studies are necessary to adequately evaluate late toxicities and efficacy.

Retrospective-Prospective Observational Study of Italian Patients Treated in Melanoma Adjuvant Cohort MAP-MADAM (Maximing ADjuvAnt MAP): Interim Analysis.

Background/Objective: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. Methods: The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective-prospective observational study that included patients who received at least one dose of D + T through the MAP. The primary endpoints were relapse-free survival (RFS) and overall survival (OS). Results: This interim analysis presents findings after the first 24 months of follow-up. A total of 310 patients were included in the study; 240 completed the 12-month treatment with D + T, while 70 discontinued the combination. RFS rates were 93.2% at 12 months and 80.2% at 24 months. The median RFS was not reached for the overall population or any subgroups. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. Conclusions: D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population.

Impact of postoperative infectious complications on long-term prognosis after esophagectomy.

Postoperative complications have been reported to be a risk factor for worse oncologic outcomes in patients with esophageal cancer. However, the impact of postoperative complications on prognosis after esophagectomy remains controversial. We aimed to investigate the factors that influence the prognosis of postoperative complications in patients who underwent oncological esophagectomy, focusing on chronic obstructive pulmonary disease (COPD). In total, 254 consecutive patients who underwent esophagectomy for esophageal cancer between 2009 and 2021 were eligible. We examined the association between postoperative complications and long-term outcomes. Focusing on infectious complications (IC: a combination of postoperative pneumonia and anastomotic leakage), overall survival (OS) and relapse-free survival (RFS) rates were significantly worse in patients with IC than those without (p<0.01, and <0.01, respectively), whereas the presence of other complications demonstrated no survival impact. No clinicopathological variables have changed the influence of IC on long-term outcomes. Meanwhile, patients with postoperative pneumonia exhibited significantly lower OS and RFS rates compared to those without in non-COPD group, however, the presence of postoperative pneumonia demonstrated no prognostic impact in COPD group. Also, interaction analysis revealed that the effect of postoperative pneumonia on poor RFS differed based on the presence of COPD (p for interaction=0.09). IC influenced the long-term outcomes in patients with esophageal cancer, however no clinicopathological variables have changed the effect of the presence of IC on prognosis. Meanwhile, the effect of postoperative pneumonia on poor survival differed based on the presence of COPD.

Indocyanine green fluorescence imaging for lymph node detection and long-term clinical outcomes in colorectal cancer surgery: A systematic review and meta-analysis.

The indocyanine green fluorescence imaging (ICG-FI) technique is increasingly being used in laparoscopic colorectal surgery for lymph node mapping. However, there is no definitive standard regarding whether the application of this technique can significantly increase the detection rate of metastatic lymph nodes and improve long-term prognosis. PubMed, Embase, Web of Science, and Cochrane Library databases were searched to include studies including ICG-FI in laparoscopic colorectal surgery. Data on the detection rate of lymph nodes, metastatic rate of ICG-positive nodes, and long-term clinical outcomes were extracted following inclusion criteria. Eighteen studies with a total of 1552 patients 922 with ICG-guided laparoscopic and 630 without ICG technique were finally included. Clinical stage II/III colorectal tumors were the most commonly studies types. The patients using the ICG-FI technique had more harvested lymph nodes (weighted mean: 23.5 vs. 18.9; WMD=4.6; p<0.00001) during dissection but a lower metastasis rate of ICG-positive nodes (61/218 [28%] vs. 96/333 [28.9%]; OR=1.45; p=0.08). Compared with conventional laparoscopic colorectal surgery, additional ICG-FI technique did not improve the 3year overall survival rate (272/289 [94.1%] vs. 269/289 [93.1%]; OR=1.19; p=0.61), relapse-free survival (246/289 [85.1%] vs. 249/289 [86.2%]; OR=0.92; p=0.72), and local recurrence rate (22/289 [7.6%] vs. 28/289 [9.7%]; OR=0.77; p=0.38). The overall detection rate of sentinel lymph nodes, lymph flow, and metastatic rate of ICG-positive nodes with the help of ICG-FI were 86.8%, 89.9%, and 22.8%, respectively. No patients experienced major adverse events during ICG injection preoperatively or postoperatively. Indocyanine green fluorescence imaging-guided procedure, compared to conventional laparoscopic dissection, can assist in obtaining a greater number of harvested lymph nodes and metastatic lymph nodes, however, it did not significantly improve the long-term clinical outcomes. Level III systematic review of randomized control and nonrandomized studies.

Prognostic Significance of Innovative Inflammation-nutrition Biomarker Score in Patients With Colorectal Cancer.

A new index, inflammation-nutrition biomarker score (INS), based on host factors, including lymphocyte to C-reactive protein ratio, C-reactive protein to albumin ratio, advanced lung cancer inflammation index, and nutritional risk index, correlated with post-operative survival time independent of the tumor, node, metastasis (TNM) stage, in a cohort of patients with various types of malignancies. Therefore, this study aimed to evaluate the prognostic value of INS in patients with colorectal cancer who underwent curative resection. We retrospectively evaluated 476 consecutive patients who underwent curative surgery for stage I-III colorectal cancer. Based on the INS definition, 240, 132, 57, 23, and 24 patients had a score of 0, 1, 2, 3, and 4, respectively. Patients with INS of 0 and 1 were classified into the low-INS group, and those with INS of 2, 3, and 4 were classified into the high-INS group. The relapse-free and overall survival rates were significantly worse in the high-INS group than in the low-INS group. Furthermore, multivariate analysis of the prognostic factors indicated that INS is an independent prognostic factor for poor relapse-free and overall survival. The combined evaluation of INS and TNM stages may allow for more accurate prognostication.