5-year OS Research Articles

Improved Overall Survival with Checkpoint Inhibition and Allogeneic Transplantation in Relapsed Hodgkin Lymphoma.

Patients with relapsed classic Hodgkin lymphomas receive salvage therapy with immune checkpoint inhibitors (ICI) or chemotherapy (no-ICI). Patients responding to therapy often undergo consolidation with allogeneic blood or marrow transplantations (alloBMT). We previously reported that relapsed cHL patients treated with ICI followed by alloBMT experienced improved 3-year progression-free survival (PFS) compared to patients treated with salvage chemotherapy without ICI, followed by alloBMT. In this retrospective analysis, we report the 5-year OS, PFS, and GVHD incidence in cHL patients treated with ICI before alloBMT with post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis. Among the 147 relapsed/refractory patients with cHL, 71 (48.3%) received ICIs and 76 (51.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. We observed an improved 5-year estimated OS of 91% (ICI) versus 66% (no-ICI), (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.16 to 0.98; P = 0.046) and a 5-year estimated PFS of 84% (ICI) versus 53% (no-ICI) (HR, 0.4; 95% CI, 0.2 to 0.81; P = 0.011). The 12-month cumulative incidence of grade III-IV GVHD was 20% (ICI) and 7% (no-ICI) (SDHR 3.16; 95% CI, 1.13 to 8.81 p = 0.03. More frequent grade III-IV acute GVHD was likely due to the higher incidence of grade III-IV acute GVHD in the subset of patients with pre-transplant exposure to ICI and shortened duration (60 days) of immunosuppression versus patients with long immunosuppression (day 180). These data suggest that cHL patients treated with ICI and alloBMT experience improved OS and the GVHD risk can be mitigated by immunosuppression until day 180.

The establishment of PD-1 inhibitor treatment prognosis model based on dynamic changes of peripheral blood indexes in patients with advanced lung squamous cell carcinoma

BackgroundUnlike patients with lung adenocarcinoma, patients with lung squamous cell carcinoma (LUSC) do not derive significant benefits from targeted therapy. In recent years, immunotherapy has revolutionized the treatment approach for LUSC. However, not all patients with this type of cancer respond to immunotherapy, necessitating the identification of effective biomarkers to predict survival prognosis and evaluate the efficacy of PD-1 inhibitors.Materials and methodsWe retrospectively collected case and hematologic data from 212 patients with advanced squamous lung cancer who received PD-1 combination therapy. Hematological indices mainly contained SCC, CEA, NSE, Hb, LDH, WBC and RBC at baseline, 6 and 12 weeks of treatment. All patients underwent imaging examinations and efficacy was evaluated according to RECIST1.1 criteria. Univariate tests were used to assess the relationship between changes in serum biomarkers, clinical characteristics and treatment outcome. The survival prognosis of patients was investigated by telephone follow-up. The optimal critical values of all hematological indicators were calculated by ROC curves, and then logistic regression and Cox regression were used to analyze multiple serum markers in relation to efficacy and survival prognosis, respectively. Finally, column line plots were constructed and validated to predict the probability of patient survival.ResultsPost-treatment RBC12w<3.81 × 10 12/L (p < 0.034) was associated with lower ORR, and WBC6w<9.34 × 109/L (p=0.041) was associated with higher DCR.SCC12w≥2.25 ng/mL (p = 0.015), NSE6w≥13.54 ng/mL(p = 0.044)and RBC0w≥4.2 × 10 9/L (p = 0.003) were independent predictors of PFS. SCC12w≥2.25 ng/mL (p < 0.001) and NSE6w≥13.54ng/mL(p = 0.042) were independent predictor of OS. Patients in the SCC12w≥2.25 ng/mL (HR = 1.943,95% CI:1.218-3.079 vs. HR = 2.161,95%CI:1.087-3.241) and NSE6w≥13.54 ng/mL (HR = 1.657,95% CI:1.118-2.535 vs. HR = 2.064,95% CI:1.569-4.169) groups had shorter PFS and OS. In subgroup analysis, patients with stage III advanced squamous lung cancer had a better pro-gnosis than those with stage IV. PD-L1-positive, and SCC12w ≥2.25 ng/mL had a worse prognosis. The results of constructing column-line plots for predicting the survival probability of 1-, 3-, and 5-year PFS and OS: The C-index and 95% CI for PFS and OS of column-line plots were 0.725 (95% CI: 0.478-1.928) and 0.755 (95% CI: 0.642-0.868), respectively, and the bootstrap correction showed a good consistency of the column-line plots.ConclusionChanges in RBC12w ≥3.81×1012/L, WBC6w ≥9.34×10 9/L, SCC12w ≥2.25 ng/mL, and NSE6w ≥13.54 ng/mL after treatment are prognostic indicators of immunotherapy in patients with advanced squamous lung cancer.

Radiation-induced nasopharyngeal necrosis combined with local recurrence in nasopharyngeal carcinoma: diagnosis and treatment strategies

ABSTRACT Background To identify the diagnosis and treatment strategies by analyzing the clinical characteristics and treatment methods of RNNCLR. Methods A total of 210 patients pathologically diagnosed with RNNCLR were retrospectively included. Clinical characteristics, MRI features, treatment methods, and survival outcomes were analyzed. Propensity score matching (PSM) analysis was performed to adjust the surgical benefit. Results Ninety-one patients (43.3%) took a single biopsy, 67 patients (31.9%) underwent repeated biopsies and 52 patients (24.8%) received endoscopic surgery to obtain pathological positive tissues. RNNCLR had characteristic imaging features distinguished from pure radiation necrosis. The interval from the previous radiotherapy was 13.2 (7.0, 23.3) months. The 1-year, 3-year, and 5-year overall survival rates were 59.6%, 32.3%, and 14.6%. Patients with reirradiation, detectable EBV-DNA level, or ICA exposure had a worse prognosis. Overall survival was significantly higher in the endoscopic surgery group than in nonsurgery group after PSM (3-year OS rates, 44.5% vs. 23.9%, p = 0.011). Conclusions Histopathological diagnosis of RNNCLR needs repeated biopsies or even surgery. Careful analysis of MRI images, correlation with interval time from last radiation, and short-term follow-up may solve the diagnostic dilemmas. Endoscopic surgery results in a survival benefit by completely resecting lesions or removing necrotic tissue to reduce necrosis-related complications.

Impact of neck dissection in cN0 patients undergoing primary or salvage total laryngectomy.

It is debatable whether neck dissection is necessary in patients with advanced laryngeal carcinoma who are clinically node-negative (cN0). We assessed the effect of neck dissection on overall survival in patients with cN0 undergoing primary or salvage laryngectomy. A retrospective evaluation of cN0 patients who underwent primary or salvage total/pharyngolaryngectomy at a French tertiary facility in 2008-2018, with or without neck dissection, was carried out. Patients were divided into two groups: primary (n = 65) and salvage (n = 84). Comparing subglottic (HR = 3.978; p = 0.023) and hypopharyngeal (HR = 2.958; p = 0.018) malignancies to other tumor subsites, the mortality rates were greater. The primary group had a greater rate of occult metastases (23.07% vs. 14.28%; p = 0.089) than the salvage. The average lymph node ratio was significantly different between the treatment groups (0.05 ± 0.04 vs. 0.17 ± 0.33; p = 0.004). If LNR > 0.05, we found poor survival rates (p < 0.001). Although performing a neck dissection during the primary treatment increased the 5-year OS rate (Yes 89.5% vs. No 83.3%; p = 0.062), there was no discernible difference in the salvage group (Yes 80.3% vs. No 78.6%; p = 0.806; Log-rank p > 0.05). For the predicted survival variables, no significant relationships were detected in the Cox regression analysis (all p-values > 0.05). Although the primary group had a greater frequency of occult metastases, neither the primary group's survival outcomes nor those of the salvage laryngectomy cases were significantly affected by neck dissection. LNR and the location of the tumor were important variables that could affect survival and the choice to do a neck dissection.

Undifferentiated uterine sarcoma : experience of a single center

ObjectivesTo investigate the clinicopathological characteristics and prognosis of patients with undifferentiated uterine sarcomas (UUS).Methods29 patients with UUS who were treated at our institution between 2001 and 2020 were analyzed.ResultsThe median age at diagnosis was 52 years (range: 26–70 years). The FIGO 2009 distribution by stage was as follows: stage I, 17 patients (58.6%); stage II, 5 patients (17.2%); stage III, 4 patients (13.8%); and stage IV, 3 patients (10.3%). For 28 patients who underwent surgical treatment, 27 patients (96.4%) underwent total/sub-radical/radical hysterectomy combined bilateral salpingo-oophorectomy, 17 (58.6%) pelvic lymphadenectomy, 7 (24.1%) para-aortic lymphadenectomy and 8 (28.6%) patients underwent omentectomy, as part of the initial surgical treatment. The median follow-up was 23.4 months (range: 4.5–200.2 months). 18 patients (62.1%) died during follow up, and 13 patients (72.2%, 13/18) died within 2 years after diagnosis. Median progression-free survival (mPFS) and overall survival (mOS) for the entire cohort were 15.5 and 27.4 months, respectively. 2-year and 5-year PFS were 40.3% and 26.9%. 2-year and 5-year OS were 54.0% and 36.5%. Stage-specific median PFS and OS were as follows: stage I-II—17.7 and 35.5 months, stage III-IV—6.0 and 6.7 months. Patients with recurrent UUS who underwent cytoreduction surgery associated with an improved overall survival (mOS: 52.9 vs. 17.9 months), but the difference was not statistically significant (P = 0.081).ConclusionsUUS are a rare group of tumors with an aggressive behavior and poor outcomes. A majority rapidly develops distant metastases despite surgical resection.

Efficacy and safety of combining anti-angiogenic therapy, radiotherapy, and PD-1 inhibitors in patients with driver gene-negative non-small cell lung cancer brain metastases: a retrospective study

BackgroundThe efficacy and safety of anti-angiogenic combination therapy in patients with driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) are uncertain.MethodsEighty-eight records of driver gene-negative patients with NSCLC treated with craniocerebral radiotherapy (RT) and programmed death factor-1 (PD-1) inhibitors between May 2021 and May 2023 were collected. Based on whether anti-angiogenic therapy (AT) is combined or not, patients are categorized into the AT group and the non anti-angiogenic therapy (NAT) group. The NAT group patients received craniocerebral RT and PD-1 inhibitor and those in the AT group received craniocerebral RT and PD-1 inhibitor with ≥ 4 cycles of AT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study.ResultsBy May 1, 2024, the iORR was 94.0% and 63.2% for AT and NAT group, respectively. The 1- and 2-year iLPFS for AT and NAT group were 93.6%, 80.9% and 69.7%, 36.4%, respectively. The 1- and 2-year iDPFS were 86.7%, 56.3% and 59.1%, 48.3%, respectively. The 1- and 2-year OS were 82.0%, 36.6% and 68.4%, 34.6%, respectively. Compared to the standard treatment (RT and PD-1 inhibitors), the addition of AT prolonged the median iLPFS (NR vs. 22.0 months, hazard ratio [HR] = 11.004, P < 0.001) and the median iDPFS (NR vs. 20.0 months, HR = 8.732, P = 0.003), but was not significant in the extension of the OS (21.0 vs. 19.0 months, HR = 1.601, P = 0.206). Multivariable analysis showed that combination therapy with AT is significantly associated with prolonged iLPFS (HR = 4.233, P = 0.002) and iDPFS (HR = 2.824, P = 0.007), whereas only GPA score is significantly associated with improved OS (HR = 0.589, P = 0.019). The incidence of hypertension in the AT group showed an increasing trend, and no significant increased risk of radiation-induced brain necrosis was found. No drug-related intracranial hemorrhage events occurred.ConclusionCombining AT, RT, and PD-1 inhibitors can substantially improve iLPFS and iDPFS for patients with driver gene-negative NSCLC with BM; however, it is not significantly associated with better OS.

From simple factors to artificial intelligence: evolution of prognosis prediction in childhood cancer: a systematic review and meta-analysis

Current paediatric cancer care requires innovative approaches to predict prognosis that facilitates personalised stratification, yet studies on the performance, composition and limitations of contemporary prognostic models are lacking. We aimed to compare the accuracy of traditional and advanced prognostic models. A systematic search for this systematic review and meta-analysis (CRTN42022370251) was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases on 28 June 2024. Studies on the accuracy of prognostic markers or models used in paediatric haematological malignancies, central nervous system (CNS), or non-CNS solid tumours (NCNSST) were included. Three model categories were defined using: 1-clinical parameters, 2-genomic-transcriptomic data, and 3-artificial intelligence (AI). Primary outcomes were area under the receiver operating characteristic curve with a 95% confidence interval (CI) for various overall survival intervals and event-free survival. Two independent groups performed selection and data extraction. We used data published by the authors and publicly available databases. Of 12,982 studies, 358 were included in the meta-analysis and 27 in the systematic review, with limited data on AI-approaches. Most data were reported on NCNSST at 5-year OS, where a statistically significant difference was observed between Category-1 (0.75 CI: 0.72-0.79) and Category-2 (0.85 CI: 0.82-0.88) (p<0.001), but not between Categories-2 and -3 (p=0.2834) (0.82 CI: 0.77-0.88). Internal validation studies showed significantly better performance compared to those using external validation, highlighting the high risk of bias (ROB) inherent in internal validation. High ROB was most commonly experienced in the outcomes and statistical analysis domains, assessed using PROBAST and QUIPS. It is advisable to introduce Category-2 and -3 models in a clinical setting, especially for NCNSST prognostic for aiding risk-stratification. Although AI-supported predictions in paediatric oncology are at an early stage of development, it is imperative to further explore their potential. This requires structured data collection and ethical sharing from paediatric oncology patients in sufficient quantity and quality. None.

Short-Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Study.

The high cost of blinatumomab in full doses of full treatments has led to dose reduction and fewer treatment cycles for most patients in China. With current needs for cost-efficiency and resource management in health care, we retrospectively evaluated the clinical effects of short-course blinatumomab treatment for R/R Ph- B-ALL at our center. Blinatumomab was administered with 24-h continuous intravenous infusion (9 μg/day for the first 3 days and 28 μg/day for 6-10 days). The clinical data of 30 R/R B-ALL patients were collected and analyzed. A total of 25 patients (83.3%) including 13 (43.3%) with a high leukemic load (> 50%) achieved morphological CR. Twelve patients (40%) were MRD-negative. The estimated 2-year OS rate was 82.62%. The 2-year PFS rate was 78.35%. The estimated 2-year OS and PFS were significantly better in patients receiving further treatment. Our findings provide novel insights into the optimization of blinatumomab therapy, proposing a viable treatment alternative that aligns with current needs for cost-efficiency and resource management in health care.

Gemcitabine Cisplatin and Durvalumab Experience in Advanced Biliary Tract Cancers: A Real-World, Multicentric Data From India.

Biliary tract cancers (BTCs) are usually diagnosed in advanced stages, where treatment options are either palliative chemotherapy and/or best supportive care. The breakthrough results of the TOPAZ-1 trial demonstrated a 24% decrease in risk of death at 2 years with the addition of durvalumab to chemotherapy. This was a multicenter retrospective cohort study conducted across 14 institutions in India. All the patients were diagnosed with advanced BTCs. The primary objective was to assess median overall survival (mOS) with the use of durvalumab in combination with chemotherapy backbone. The patient details, treatment details, laboratory results, and outcome parameters were recorded from the prospectively collected databases. A total of 148 patients were included with a median age of 57.5 years; 36 (24.3%) patients had borderline Eastern Cooperative Oncology Group performance status ≥2. The most common subtype was gall bladder cancer (GBC), seen in 94 patients (63.5%); 126 (85.1%) patients presented with de novo metastases. At a median follow-up of 6.8 months (95% CI, 5.9 to 7.8), the estimated mOS for the entire cohort was 12 months (95% CI, 7.8 to 16.3) and median progression-free survival was 8.2 months (95% CI, 7.1 to 9.4) with objective response achieved in 44 (29.7%) patients, and the estimated 2-year OS being 25%. Immune-related grade 3/4 adverse events were reported in 11 (7.4%) patients. In multivariate analysis, age <60 years (P = .001) and standard dose of durvalumab (P < .001) were found to have improved OS compared with age >60 years and low dose of durvalumab. To our knowledge, these real-world data provide the first evidence in Indian context of the efficacy and safety of durvalumab plus chemotherapy in patients with advanced/metastatic BTCs especially in GBC.

Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in a randomised trial of systemic therapy in early-stage follicular lymphoma

We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95% CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95% CI=0.16-1.18, p=0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95% CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95% CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95% CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Clonal evolution defines risk stratification for central nervous system leukemia in adult acute lymphoblastic leukemia.

It is well established that central nervous system leukemia (CNSL) is an adverse prognostic factor in acute lymphoblastic leukemia (ALL), yet whether prognostic heterogeneity reside in CNSL is less addressed. Therefore, we aimed to develop potential risk classification for CNSL. We retrospectively analyzed a study in PDT-ALL-2016 pediatric-inspired cohort (N = 494). Flow cytometry (FCM) and next-generation sequencing (NGS) were tested on bone marrow (BM) and cerebrospinal fluid (CSF). The 5-year OS of 437 non-CNSL patients was 62.3% and 33.7% in 57 CNSL patients (P < 0.001). 57 CNSL including 16 primary CNS involvement and 41 CNS relapse patients were divided into 3 groups. The 5-year OS was 48.9% in patients with concordant FCM and NGS between BM and CSF, which were defined as non-clonal evolutionary CNSL, a standard-risk subgroup, while the 5-year OS was 30.2% in patients with discordant FCM or NGS between BM and CSF and isolated CNS relapse (P < 0.05), which were defined as clonal evolutionary CNSL, a high-risk subgroup. Furthermore, the mean times of lumbar punctures to achieve complete remission (CR) in CSF was 4.14 in clonal evolutionary CNSL, comparing to 1.62 in non-clonal evolutionary CNSL (P < 0.05). Based on the evidence of clonal evolution, we develop a risk stratification for CNSL for the first time.

A systematic review of stereotactic radiosurgery for metastatic spinal sarcomas.

Sarcomas metastasizing to the spine are a rare entity. Ideally an En-bloc resection is necessary to achieve durable local control (LC) rates. However, anatomical constraints often limit the degree of tumor resection. Because of this, other therapeutic modalities either replacing or as an adjuvant to resection are necessary. Stereotactic radiosurgery (SRS) is a reasonable candidate therapy. We conducted a systematic review of the literature using the following databases: PubMed, Science Direct, and Cochrane library. We used a combination of the following terms connected by boolean operators: "Metastatic Sarcoma, Sarcoma of the Spine, Spine Sarcoma, Metastasis, stereotactic radiosurgery, SRS." All retrospective and prospective cohorts, as well as randomized control trials reporting on patients with histopathologically confirmed metastatic sarcomas of the bony elements of the vertebrae, thecal sac, cord, or associated soft tissues of the spine were included. We excluded animal studies, case reports, case series, patients < 18 (pediatric cohorts), review articles and meta-analyses. No date filters were applied to our search. Our final analysis included 5 studies ranging from 2009 to 2024 reporting on 260 patients and 371 associated lesions. Leiomyosarcoma was the most frequently reported histologic subtype (60%). Most lesions were localized to the thoracic spine (48.6%). 75% of studies reported a median dose < 30Gy, and achieved biologically equivalent doses (BEDs) ranging from < 50-100. Pooled 1-year median survival was 64.5% (IQR: 61.8-75.10). Pooled 1-year median LC was 86% (IQR: 79.4-88.5). Three of five studies (60%) for OS and 4/5 (80%) for LC had data availability suitable for meta-analysis. The 1-year OS and LC rates proportions across these studies were 67% (proportion = 0.67, 95% CI: 0.57-0.75, p = 0.07, I2 = 63%), and 84% (proportion = 0.84, 95% CI: 0.78-0.89, p = 0.10, I2 = 52%) respectively. Median follow up across all studies was 18 months (IQR:12.7-31.3). SRS is a reasonable alternative therapy in either the up front, salvage or adjuvant setting which can facilitate durable LC.

MiR-200 family as new potential prognostic factor of overall survival of patients with WHO G2 and WHO G3 brain gliomas

Gliomas are the predominant cause of cancer-related deaths among the young population. Even after incorporation of IDH1/2 mutations and 1p19q codeletion there are doubts regarding adjuvant treatment in WHO G2/G3 gliomas. miRNA molecules control about 30% of all genes, also many oncogenes, tumor suppressor genes and genes responsible for the response to ionizing radiation and systemic treatment. Patients with brain gliomas exhibit miRNA disorders. We aimed to evaluate the expression of miR-200 family members in relation to selected clinico-pathological factors and their prognostic value. We enrolled 53 patients diagnosed with WHO G2/G3 brain gliomas treated between 2012–2016. RT-qPCR based expression of miR-200 family was assessed in tumor and surrounding non-cancerous tissue. An analysis of selected clinico-pathological features was carried out. A logistic regression model was prepared for the miRNA signature. The predictive potential of the signature was assessed using the ROC curve. A stepwise backward regression model was used to select variables with a significant predictive potential related to OS. It was shown that miR-200a-3p, miR-200a-5p, miR-200c-5p, miR-141-3p and miR-429 can be independent predictors of survival. Better 2- and 5-year OS was associated with higher expression of miR-200a-3p, miR141-3p and lower expression of miR-200a-5p, miR-200c-5p, miR-429. The strongest predictors of survival were miR-200a-5p, miR-200b-3p, miR-200c-5p, miR-141-3p, miR-429, tumor volume and CTV. Members of the miR-200 family exhibit prognostic value for 2- and 5-year OS. Presented predictive models of survival may be clinically useful for treatment optimization.

Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer

PurposeOur perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older.MethodsThis was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined.ResultsThe median age of the 71 patients (34 males, 37 females) was 78 (75–92) years, and their median body mass index (BMI) was 22.3 (13.4–31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15).ConclusionThe SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use.

Strategies for Recurrent Colorectal Liver Metastases Based on Prognostic Factors and Resectability: Potential Benefit of Multidisciplinary Treatment.

Colorectal liver metastasis (CLM) is classified into technical and oncologic categories, with recommended treatments for each resectability category. However, the classification of recurrent CLM has not been established to date. This study evaluated patients with CLM who underwent initial liver resection between 2006 and 2020 and subsequently experienced liver recurrence. Long-term outcomes and prognostic factors associated with recurrent CLM were investigated. From 949 patients who underwent an initial liver resection, the analysis included 392 patients with liver recurrence. Repeat liver resection was associated with a significantly longer prognosis than non-resection (5-year overall survival [OS] from initial liver resection: 66.3 % vs 27.2 %, p < 0.0001). Multivariable analysis indicated the following independent prognostic factors: four or more recurrent tumors (p = 0.015), tumor 5 cm or larger in size (p = 0.004), and presence of extrahepatic diseases (p = 0.003). The patients were stratified into resectable, borderline resectable, and unresectable recurrent CLM groups based on these criteria. The prognosis varied significantly across the groups, with 5-year OS rates of 67.3 % for resectable recurrent CLM, 30.8 % for borderline resectable recurrent CLM, and 2.6 % for unresectable recurrent CLM (p < 0.0001). Patients with borderline resectable recurrent CLM who did not receive adjuvant chemotherapy after initial liver resection had a positive prognostic impact of preoperative chemotherapy (p = 0.049). The significant independent predictors of recurrent CLM prognosis were four or more tumors, tumor size of 5 cm or larger, and the presence of extrahepatic diseases at recurrence. It is critical to onsider the current condition and tumor resectability at the time of recurrence, and tailored treatments could further improve recurrent CLM outcomes.

Differences in the epidemiology and survival of patients with colorectal cancer between China and the United States: a large cross-sectional study.

Studying the epidemiological and management characteristics of colorectal cancer (CRC) between China and the US has important implications. The present cross-sectional study included patients from SEER and Southwest China Colorectal (SCC) databases. Incidence, treatment and survival information were compared between two countries.86859 patients in the SEER database and 5838 patients in the SCC database were included. The estimated incidence of CRC in the US was greater than that in China from 2006 to 2019. The most common tumor sites of CRC patients in China were the RSC (66.5%), RCC (20.2%) and LCC (13.3%), while those in the US were the RCC (44.4%), RSC (29.8%) and LCC (25.8%). Chinese CRC patients were more likely to be male (58.9% vs 52.4%, p < 0.001), have a greater stage II CRC rate (49.8% vs 27.8%, p < 0.001), younger age at diagnosis (median 64 vs 66years, p < 0.001). Radical surgery rates were lower in Chinese RCC (92.3% vs 93.9%, p < 0.001) and LCC (88.9% vs 92.0%, p < 0.001) patients. The adjuvant therapy rates were lower in Chinese CRC patients. The 5-year overall survival rates were 71.8% and 78.2% for Chinese and US CRC patients, respectively (p < 0.001).China is undergoing an increasing incidence of CRC. The treatment and mortality of CRC differ in China and US populations. China had a lower adjuvant therapy rate and a lower 5-year OS rate compared with the US.

Short- and long-term outcomes following perioperative ERAS management in patients undergoing minimally invasive radical gastrectomy after neoadjuvant chemotherapy: A single-center retrospective propensity score matching study

IntroductionGastric cancer patients receiving neoadjuvant chemotherapy (NACT) are more vulnerable to perioperative stress. Enhanced recovery after surgery (ERAS) is widely used in surgical patients aiming at reducing stress responses. However, whether this approach is safe and feasible for gastric cancer patients received minimally invasive radical gastrectomy after NACT remained determined. So, the objective of this study is to investigate the effects of ERAS for this special group of gastric cancer patients. Material and methodsThe data of gastric cancer patients who underwent minimally invasive radical gastrectomy after NACT were collected. Patients were divided into an ERAS group and a conventional group based on whether they received perioperative ERAS management. Propensity score matching was conducted to eliminate bias. Pre- and postoperative inflammatory and nutritional marker levels, postoperative complications, recovery indices and 3-year OS and RFS were observed. ResultsA total of 252 patients were analyzed after 1:1 PSM, including 126 patients in the ERAS group and 126 in the conventional group. The results showed that the implementation of ERAS significantly reduced the levels of novel inflammatory indicators, improve nutritional status and accelerate postoperative recovery. We found that the 3-year OS (72.2 % vs. 66.7 %) and RFS (67.5 % vs. 61.9 %) in the ERAS group showed an improvement trend compared to those in the traditional group, especially for stage III patients, although these differences were not significant. ConclusionThe perioperative ERAS program is safe and feasible for gastric cancer patients received minimally invasive radical gastrectomy after NACT.

Phase I Study of Adjuvant Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine, Low Dose Cyclophosphamide, and SBRT followed by FFX in High-Risk Resected Pancreatic Ductal Adenocarcinoma

PurposeLocal and distant progression remain common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase I trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy) and SBRT followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC. Patients and MethodsThe study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full dose FFX. After toxicity review, cohort 2 had SBRT and were switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression. Results19 patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after two cycles of mFFX. Median OS/DFS for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. 1-year and 2-year OS for cohort 3 was 83%/75%, respectively. At last follow-up (median= x), 5 patients were alive (42%) in cohort 3. ConclusionThis is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

Pre-transplant metabolic tumor volume predicts recurrence following liver transplantation for colorectal metastasis: A multicenter study.

Liver transplant (LT) for colorectal cancer liver metastases (CRLM) is increasingly popular, yet the ideal selection criteria remain unknown. Pre-transplant PET metabolic tumor volume (MTV) has been described as predicting recurrence, with a proposed cut-off of MTV ≥70cm3. This approach has not been validated. Patients undergoing LT for CRLM at two academic transplant centers (1/1/2017-12/1/2023) were included. PET-MTV was calculated by a staff radiologist from the most recent PET-scan before LT using the published protocol. Twenty-six patients were included. Median follow-up was 609 days (IQR 320-1069) and from PET to LT was 1.9 months (1.3-2.6). Nearly all (n=24, 92.3%) received living donor transplantation. Absolute recurrence rate was 30.8% (n=8). Actuarial unadjusted 1-, and 2-year RFS were 83% (n=15/18), and 62% (n=8/13); 1- and 2-year OS were 100% (n=18/18), and 85% (n=11/13).The incidence of recurrence-per-year follow-up was 0.35 when MTV ≥70cm3 versus 0.10 if MTV <70cm3 (P<0.001). Median RFS using Kaplan-Meier product-estimate was 0.83 years (95%CI 0.43-1.23) in MTV≥70cm3 versus 4.1 years (95%CI 2.90-5.22) when MTV<70cm3 (P<0.001); this was also associated with improved OS (P=0.003). MTV>70cm3 demonstrated HR=2.42 (95%CI 2.2-62.2, P=0.006) for association with RFS on univariate Cox-proportional hazards analysis, and an Area-Under-the-Curve (AUC)=0.771 (95%CI 0.560-0.981) for predicting recurrence (P=0.030)Nineteen patients (69.2%) had histologically viable tumor, which was associated with recurrence (43% vs. 0%, P=0.039) and reduced RFS (log-rank P=0.019). PET-MTV was associated with presence of histologically-viable tumor (AUC=0.763, 95%CI 0.583-0.944). PET-MTV ≥70cm3 was associated with reduced RFS and OS after LT for CRLM, confirming findings from the Norway group. This is likely due to its' ability to identify residual viable tumors, which are independently associated with recurrence. PET-MTV should be a key selection criterion prior to LT for CRLM.

CTNI-25. TUMOR TREATING FIELDS (TTFIELDS) THERAPY WITH CHEMORADIATION, FOLLOWED BY MAINTENANCE TTFIELDS THERAPY/TEMOZOLOMIDE (TMZ), IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM). RESULTS OF PHASE II CLINICAL STUDY

Abstract INTRODUCTION Tumor-Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cancer cell function and tumor progression via a multimodal mechanism of action. Following the phase 3 pivotal EF-14 study, TTFields therapy concomitant with temozolomide (TMZ) maintenance therapy became approved for newly-diagnosed glioblastoma (ndGBM). Pre-clinical data and pilot clinical studies suggests synergistic effect of concomitant TTFields treatment with radiotherapy (RT). OBJECTIVE To assess the efficacy and safety of first line TTFields therapy concomitant with RT/TMZ vs RT/TMZ alone in adult patients with ndGBM. Design: 69 patients with ndGBM and KPS≥70 stratified by MGMT status, extent of resection, and age, were randomized 1:1. The experimental arm received TTFields therapy from the first day of chemoradiation, the control arm started 4 weeks after completion of chemoradiation. Patients continued TTFields therapy until second disease progression or 24months. The primary endpoint was 1-year PFS rate, and secondary endpoints included PFS, OS, and safety. Kaplan-Meier estimates were used to assess whether PFS and OS were improved with first line TTFields therapy/RT/TMZ vs RT/TMZ with delayed TTFields therapy. RESULTS Overall, 46 patients received maintenance chemotherapy and TTFields therapy. Mean age was 62 years (range:27–77). One-year PFS rate was 36% and 19% in the experimental and control arms, respectively (p-value=0.10). Median PFS was 9.9 and 5.6 months (HR 0.53, p-value 0.049). Median OS was 25.9 and 17 months (HR 0.85, p-value=0.6). Two-year OS rates were 52% and 31% (p-value 0.07). Among patients with high TTFields usage (≥75%) 2-year OS rates were 78% and 34% (p=0.01). CONCLUSIONS The addition of concomitant TTFields to standard treatment with temozolomide and RT for patients with ndGBM appears to be another step in improving the outcome of this patients population. This is further investigated in the large-scale TRIDENT study.