Electronic health intervention to manage symptoms of immunotherapy in patients with cancer (SOFIA): Results from a randomized controlled pilot trial.

BACKGROUND: For patients receiving immune checkpoint inhibitors, early detection of immune-related adverse events (irAEs) is critical for one's safety. To this end, a smartphone app (SOFIA) was developed that featured the assessment of electronic patient-reported outcomes (ePROs) focusing on irAEs as well as a set of comprehensive supportive information. Its feasibility and preliminary efficacy were evaluated in a randomized controlled trial (RCT). METHODS: Patients who received immune checkpoint inhibition therapy were randomly assigned to an intervention group (IG) or a control group (CG; care as usual). During the 12-week intervention period, IG patients used SOFIA to report twice weekly ePROs and receive cancer- and immunotherapy-relevant contents. Before a patient's next clinical visit, the physician in charge was given the ePRO reports. The primary objective was to test the feasibility of SOFIA. Furthermore, the preliminary efficacy of SOFIA for health-related quality of life (HRQOL), psychosocial outcomes, and medical data was examined. Clinical outcomes were assessed at baseline (T0), post-intervention (T1), and a 3-month follow-up (T2). RESULTS: Seventy-one patients were randomized to the IG (n = 34) or the CG (n = 37). SOFIA showed high feasibility and acceptance. At T1, patients in the IG reported significantly better HRQOL and role functioning and less depression, distress, and appetite loss. No significant differences were revealed regarding medical data, the utilization of supportive care services, or survival. CONCLUSIONS: SOFIA showed high feasibility and acceptance and improved HRQOL and psychosocial outcomes. These results suggest further evaluation of efficacy in a large-scale confirmatory multicenter RCT.

Prognostic Relevance of the Proximal Resection Margin Distance in Distal Gastrectomy for Gastric Adenocarcinoma.

BACKGROUND: The risk for recurrence in patients with distal gastric cancer can be reduced by surgical radicality. However, dispute exists about the value of the proposed minimum proximal margin distance (PMD). Here, we assess the prognostic value of the safety distance between the proximal resection margin and the tumor. PATIENTS AND METHODS: This is a single-center cohort study of patients undergoing distal gastrectomy for gastric adenocarcinoma (2001-2021). Cohorts were defined by adequacy of the PMD according to the European Society for Medical Oncology (ESMO) guidelines (≥ 5 cm for intestinal and ≥ 8 cm for diffuse Laurén's subtypes). Overall survival (OS) and time to progression (TTP) were assessed by log-rank and multivariable Cox-regression analyses. RESULTS: Of 176 patients, 70 (39.8%) had a sufficient PMD. An adequate PMD was associated with cancer of the intestinal subtype (67% vs. 45%, p = 0.010). Estimated 5-year survival was 63% [95% confidence interval (CI) 51-78] and 62% (95% CI 53-73) for adequate and inadequate PMD, respectively. Overall, an adequate PMD was not prognostic for OS (HR 0.81, 95% CI 0.48-1.38) in the multivariable analysis. However, in patients with diffuse subtype, an adequate PMD was associated with improved oncological outcomes (median OS not reached versus 131 months, p = 0.038, median TTP not reached versus 88.0 months, p = 0.003). CONCLUSION: Patients with diffuse gastric cancer are at greater risk to undergo resection with an inadequate PMD, which in those patients is associated with worse oncological outcomes. For the intestinal subtype, there was no prognostic association with PMD, indicating that a distal gastrectomy with partial preservation of the gastric function may also be feasible in the setting where an extensive PMD is not achievable.

The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients.

BACKGROUND & AIMS: Owing to the high load of immunogenic frameshift neoantigens, tumors arising in individuals with Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, are characterized by a pronounced immune infiltration. However, the immune status of normal colorectal mucosa in LS is not well characterized. We assessed the immune infiltrate in tumor-distant normal colorectal mucosa from LS CRC patients, sporadic microsatellite-unstable (MSI) and microsatellite-stable (MSS) CRC patients, and cancer-free LS carriers. METHODS: CD3-positive, FOXP3-positive, and CD8-positive T cells were quantified in, respectively, 219, 233, and 201 formalin-fixed paraffin-embedded (FFPE) normal colonic mucosa tissue sections from CRC patients and cancer-free LS carriers and 26, 22, and 19 LS CRCs. CD3-positive T cells were also quantified in an independent cohort of 97 FFPE normal rectal mucosa tissue sections from LS carriers enrolled in the CAPP2 clinical trial. The expression of 770 immune-relevant genes was analyzed in a subset of samples with the use of the NanoString nCounter platform. RESULTS: LS normal mucosa specimens showed significantly elevated CD3-, FOXP3-, and CD8-positive T-cell densities compared with non-LS control specimens. Gene expression profiling and cluster analysis revealed distinct immune profiles in LS carrier mucosa with and without cancer manifestation. Long-term follow-up of LS carriers within the CAPP2 trial found a correlation between mucosal T-cell infiltrate and time to subsequent tumor occurrence. CONCLUSIONS: LS carriers show elevated mucosal T-cell infiltration even in the absence of cancer. The normal mucosa immune profile may be a temporary or permanent tumor risk modifier in LS carriers.

Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective.

PURPOSE: According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution. METHODS: Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups. RESULTS: Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023). CONCLUSION: Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings.

Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, unpleasant and usually long-lasting side effect of neurotoxic chemotherapeutic agents. This study aimed to investigate the preventive potential of sensorimotor- (SMT) and resistance training (RT) on CIPN. METHODS: Patients (N = 170) were randomised to SMT, RT or usual care (UC). Both exercise groups trained 3×/week for a total of 105 min/week during neurotoxic chemotherapy (mean length: 20 weeks). Before and 3 weeks after neurotoxic chemotherapy, CIPN signs/symptoms were assessed via Total Neuropathy Score (TNSr; primary endpoint) and EORTC QLQ-CIPN15 questionnaire. In addition, balance (centre of pressure), muscle strength (isokinetic), quality of life (QoL, EORTC QLQ-C30) and relative chemotherapy dose intensity (RDI) were investigated. The follow-up period covered 6 months after the end of chemotherapy. RESULTS: Intention-to-treat analyses (N = 159) revealed no differences regarding CIPN signs/symptoms. Exploratory per-protocol analyses (minimum training attendance rate 67%; N = 89) indicated that subjectively perceived sensory symptoms in the feet increased less during chemotherapy in the adherent exercisers (pooled group: SMT+RT) than in the UC group (-8.3 points (-16.1 to -0.4); P = 0.039, ES = 1.27). Furthermore, adherent exercisers received a higher RDI (96.6 ± 4.8 vs. 92.2 ± 9.4; P = 0.045), showed a better course of muscular strength (+20.8 Nm (11.2-30.4); P < 0.001, ES = 0.57) and QoL (+12.9 points (3.9-21.8); P = 0.005, ES = 0.64). During follow-up, CIPN signs/symptoms persisted in all groups. CONCLUSIONS: This study demonstrates that SMT and/or RT alleviate subjectively perceived sensory CIPN symptoms in the feet and other clinically relevant cancer therapy-related outcomes, if an appropriate training stimulus is achieved. CLINICAL TRIAL REGISTRATION: NCT02871284.

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours. METHODS: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group. INTERPRETATION: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.

Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease.

BACKGROUND: Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance. METHODS: Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER). RESULTS: We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion. CONCLUSION: Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study.

Prognostic significance of microsatellite-instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy.

Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal-junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse-free survival and overall survival were calculated and correlated with MSI status. We identified the MSI-H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI-H patients, overall survival was significantly better for patients with MSI-H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log-rank test p = 0.014). Among MSI-H patients, an unexpected long-term survival after relapse was observed. Our data indicate that the MSI-H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI-H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI-H tumors should be considered.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial.

BACKGROUND: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

Neoadjuvant Therapy Improves Outcomes in Locally Advanced Signet-Ring-Cell Containing Esophagogastric Adenocarcinomas.

BACKGROUND: Only a few studies have analyzed multimodal treatment concepts in the subgroup of signet-ring-cell containing upper gastrointestinal (GI) cancer. Recent retrospective, multicentric data favor primary resection without neoadjuvant chemotherapy for gastric signet-ring-cell containing carcinomas (SRCs). We compared the outcomes of primarily resected carcinomas with neoadjuvantly treated, locally advanced esophagogastric SRCs. METHODS: A total of 310 patients with esophagogastric SRC-staged cT3/4/Nany/Many from a prospective unicentric database were included in this study; 192 (61.9%) received neoadjuvant therapy (NEO group) and 118 (38.1%) were primarily resected (RES group). RESULTS: Overall, 128 (41.3%) patients presented with adenocarcinoma of the esophagogastric junction (AEG) and 182 (58.7%) presented with gastric cancer. Neoadjuvant therapy was significantly associated with resection in curative intent (NEO: 91.1%; RES: 75.4%; P = 0.001), improved (y)pT category (P = 0.035), improved (y)pN category (P < 0.001), and R0 resections (curative intent cohort: 76.0% in NEO vs. 60.7% in RES; P = 0.010), among others, but not with postoperative complications. Overall survival was significantly improved by neoadjuvant treatment {median survival 28.5 months (95% confidence interval [CI] 14.4-39.6) vs. RES: 14.9 months (10.6-17.5); P < 0.001}, as well as in subgroups (AEG and gastric tumors, R0-resected patients, and patients with and without relevant comorbidities). Independent prognostic factors were neoadjuvant therapy (hazard ratio [HR] 0.66; P = 0.023), pT4 category (HR 1.71; P = 0.041), pN2 category (HR 1.86; P = 0.013), pN3 category (HR 2.40; P < 0.001), pM1 category (HR 1.95; P = 0.003), age > 70 years (HR 1.79; P = 0.006), gastric localization (HR 0.69; P = 0.032), American Society of Anesthesiologists classification 3/4 (HR 1.71; P = 0.004), and incomplete resection R1/2 (HR 1.6; P = 0.014). CONCLUSIONS: Our results demonstrate a survival advantage for advanced-stage esophagogastric SRC patients by neoadjuvant treatment.

Postoperative follow-up programs improve survival in curatively resected gastric and junctional cancer patients: a propensity score matched analysis.

BACKGROUND: To date there is no evidence that more intensive follow-up after surgery for esophagogastric adenocarcinoma translates into improved survival. This study aimed to evaluate the impact of standardized surveillance by a specialized center after resection on survival. METHODS: Data of 587 patients were analyzed who underwent curative surgery for esophagogastric adenocarcinoma in our institution. Based on their postoperative surveillance, patients were assigned to either standardized follow-up (SFU) by the National Center for Tumor Diseases (SFU group) or individual follow-up by other physicians (non-SFU group). Propensity score matching (PSM) was performed to compensate for heterogeneity between groups. Groups were compared regarding clinicopathological findings, recurrence, and impact on survival before and after PSM. RESULTS: Of 587 patients, 32.7% were in the SFU and 67.3% in the non-SFU group. Recurrence occurred in 39.4% of patients and 92.6% within the first 3 years; 73.6% were treated, and of those 17.1% underwent resection. In recurrent patients overall and post-recurrence survival (OS/PRS) was influenced by diagnostic tools (p < 0.05), treatment (p ≤ 0.001), and resection of recurrence (p ≤ 0.001). Standardized follow-up significantly improved OS (84.9 vs. 38.4 months, p = 0.040) in matched analysis and was an independent positive predictor of OS before and after PSM (p = 0.034/0.013, respectively). CONCLUSION: After PSM, standardized follow-up by a specialized center significantly improved OS. Cross-sectional imaging and treatment of recurrence were associated with better outcome. Regular follow-up by cross-sectional imaging especially during the first 3 years should be recommended by national guidelines, since early detection might help select patients for treatment of recurrence and even resection in few designated cases.

Surgical strategies in true adenocarcinoma of the esophagogastric junction (AEG II): thoracoabdominal or abdominal approach?

BACKGROUND: The optimal surgical approach for adenocarcinoma directly at the esophagogastric junction (AEG II) is still under debate. This study aims to evaluate the differences between right thoracoabdominal esophagectomy (TAE) (Ivor-Lewis operation) and transhiatal extended gastrectomy (THG) for AEG II. METHODS: From a prospective database, 242 patients with AEG II (TAE, n = 56; THG, n = 186) were included and analyzed according to characteristics and perioperative morbidity and mortality and overall survival (chi-square, Mann-Whitney U, log-rank, Cox regression). RESULTS: Groups were comparable at baseline with exception of age. Patients older than 70 years were more frequently resected by THG (p = 0.003). No differences in perioperative morbidity (p = 0.197) and mortality (p = 0.711) were observed, including anastomotic leakages (p = 0.625) and pulmonary complications (p = 0.494). There was no significant difference in R0 resection (p = 0.719) and number of resected lymph nodes (p = 0.202). Overall median survival was 38.4 months. Survival after TAE was significantly longer than after THG (median OS not reached versus 33.6 months, p = 0.02). Multivariate analysis revealed pN-category (p < 0.001) and type of surgery (p = 0.017) as independent prognostic factors. The type of surgery was confirmed as prognostic factor in locally advanced AEG II (cT 3/4 or cN1), but not in cT1/2 and cN0 patients. CONCLUSIONS: Our single-center experience suggests that patients with (locally advanced) AEG II tumors may benefit from TAE compared to THG. For further evaluation, a randomized trial would be necessary.

Perioperative Chemotherapy in Elderly Patients with Locally Advanced Adenocarcinoma of the Stomach and the Esophagogastric Junction: A Retrospective Cohort Analysis of Toxicity and Efficacy at the National Center for Tumor Diseases, Heidelberg.

OBJECTIVE: Esophagogastric cancer occurs more frequently in older patients, but these are underrepresented in clinical studies establishing the current treatment standards for perioperative chemotherapy in locally advanced disease. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens. METHODS: Using a prospectively generated database, we analyzed 63 patients aged ≥70 years undergoing perioperative chemotherapy for locally advanced esophagogastric cancer. The information included Eastern Cooperative Oncology Group (ECOG) performance status, comorbidity index, body mass index, regimen of chemotherapy, toxicity, dosage adjustments, date of surgery, application of adjuvant treatment, date of progression, and date of death. Survival times were calculated. RESULTS: The median age was 73 years. 96.8% of the patients received an oxaliplatin-containing regimen. In 17.5% of the patients, the dosage was reduced, and treatment was previously permanently stopped in 7.9%; 80% of the patients underwent curatively intended surgery, but only 27.5% of those undergoing resection started adjuvant treatment. Major histological regression was observed in 21.6% of the patients. The median survival was 19.1 months. Significantly improved survival times were observed for patients undergoing surgery (p = 0.008) and for patients with a triplet therapy (p = 0.004). Survival was worse for patients aged ≥75 years. CONCLUSION: perioperative treatment is feasible and effective in elderly patients with esophagogastric cancer.

Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer - the multinational MATEO study.

BACKGROUND: The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. METHODS: The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. DISCUSSION: MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. TRIAL REGISTRATION: NCT02128243 (date of registration: 29-04-2014).

Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient.

BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. METHODS: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients. RESULTS: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients. CONCLUSION: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient's performance status and comorbidities.

Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial.

BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection. METHODS: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m2 on day 1, intravenous cisplatin 60 mg/m2 on day 1, and either fluorouracil 200 mg/m2 as continuous intravenous infusion or capecitabine 1250 mg/m2 orally (two doses of 625 mg/m2 per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, intravenous oxaliplatin 85 mg/m2, intravenous leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2 as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). INTERPRETATION: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma. FUNDING: None.

Outcomes and risk factors for cancer patients undergoing endoscopic intervention of malignant biliary obstruction.

BACKGROUND: Malignant bile duct obstruction is a common problem among cancer patients with hepatic or lymphatic metastases. Endoscopic retrograde cholangiography (ERC) with the placement of a stent is the method of choice to improve biliary flow. Only little data exist concerning the outcome of patients with malignant biliary obstruction in relationship to microbial isolates from bile. METHODS: Bile samples were taken during the ERC procedure in tumor patients with biliary obstruction. Clinical data including laboratory values, tumor-specific treatment and outcome data were prospectively collected. RESULTS: 206 ERC interventions in 163 patients were recorded. In 43 % of the patients, systemic treatment was (re-) initiated after successful biliary drainage. A variety of bacteria and fungi was detected in the bile samples. One-year survival was significantly worse in patients from whom multiresistant pathogens were isolated than in patients, in whom other species were detected. Increased levels of inflammatory markers were associated with a poor one-year survival. The negative impact of these two factors was confirmed in multivariate analysis. In patients with pancreatic cancer, univariate analysis showed a negative impact on one-year survival in case of detection of Candida species in the bile. Multivariate analysis confirmed the negative prognostic impact of Candida in the bile in pancreatic cancer patients. CONCLUSION: Outcome in tumor patients with malignant bile obstruction is associated with the type of microbial biliary colonization. The proof of multiresistant pathogens or Candida, as well as the level of inflammation markers, have an impact on the prognosis of the underlying tumor disease.

Analysis of Burnout Prevalence among German Physicians Working in a Palliative Care Setting: A Survey of the AIO Quality of Life Working Group.

INTRODUCTION: Palliative care physicians (Pcps) face special challenges caring for terminally ill patients. We conducted this study to evaluate the burnout (bo) prevalence among pcps and sought to identify risk as well as protective factors as a basis for the development of preventive measures. METHODS: Participants (Pcs) were invited via e-mail to complete an online survey between May and June 2022. Besides the Oldenburg Burnout Inventory assessing the bo dimensions of exhaustion (exh) and disengagement (dis), sociodemographic data were collected. RESULTS: The study found that 58% (cut-off mean value [M] ≥2.18) or more specifically, 38% (cut-off M ≥2.5) of the pcs showed increased scores in the exh subscale as a key dimension of bo. All dimensions were correlated with the level of medical and palliative care training, with higher scores for physicians in training. Furthermore, pcs without preventive measures like employee appraisals at work were more likely to be considered exhausted, disengaged, or burned out. The discrepancy between high exh and low dis scores shows that the polled pcps, despite feeling exh, nevertheless considered their work meaningful. CONCLUSION: Bo prevalence among pcps exceeds that of the general population and other specialties, whereas inexperienced pcps might be at high risk of shifting from exh to bo and could therefore benefit from tailored support. Further preventive measures including individual and organizational aspects are necessary to prevent bo and promote health among medical staff, thereby preserving quality of patient care. Elementary preventive measures such as employee appraisals can have a protective effect against bo.