German, Austrian, and Swiss guidelines for systemic treatment of gastric cancer.

The updated edition of the German, Austrian and Swiss Guidelines for Systemic Treatment of Gastric Cancer was completed in August 2023, incorporating new evidence that emerged after publication of the previous edition. It consists of a text-based "Diagnosis" part and a "Therapy" part including recommendations and treatment algorithms. The treatment part includes a comprehensive description regarding perioperative and palliative systemic therapy for gastric cancer and summarizes recommended standard of care for surgery and endoscopic resection. The guidelines are based on a literature search and evaluation by a multidisciplinary panel of experts nominated by the hematology and oncology scientific societies of the three involved countries.

Adjuvant treatment recommendations for patients with ER-positive/HER2-negative early breast cancer by Swiss tumor boards using the 21-gene recurrence score (SAKK 26/10).

BACKGROUND: To evaluate the effect of Recurrence Score® results (RS; Oncotype DX® multigene assay ODX) on treatment recommendations by Swiss multidisciplinary tumor boards (TB). METHODS: SAKK 26/10 is a multicenter, prospective cohort study of early breast cancer patients: Eligibility: R0-resection, ≥10% ER+ malignant cells, HER2-, pN0/pN1a. Patients were stratified into low-risk (LR) and non-low-risk (NLR) groups based on involved nodes (0 vs 1-3) and five additional predefined risk factors. Recommendations were classified as hormonal therapy (HT) or chemotherapy plus HT (CT + HT). Investigators were blinded to the statistical analysis plan. A 5%/10% rate of recommendation change in LR/NLR groups, respectively, was assumed independently of RS (null hypotheses). RESULTS: Two hundred twenty two evaluable patients from 18 centers had TB recommendations before and after consideration of the RS result. A recommendation change occurred in 45 patients (23/154 (15%, 95% CI 10-22%) in the LR group and 22/68 (32%, 95% CI 22-45%) in the NLR group). In both groups the null hypothesis could be rejected (both p < 0.001). Specifically, in the LR group, only 5/113 (4%, 95% CI 1-10%) with HT had a recommendation change to CT + HT after consideration of the RS, while 18/41 (44%, 95% CI 28-60%) of patients initially recommended CT + HT were subsequently recommended only HT. In the NLR group, 3/19 (16%, 95% CI 3-40%) patients were changed from HT to CT + HT, while 19/48 (40%, 95% CI 26-55%) were changed from CT + HT to HT. CONCLUSION: There was a significant impact of using the RS in the LR and the NLR group but only 4% of LR patients initially considered for HT had a recommendation change (RC); therefore these patients could forgo ODX testing. A RC was more likely for NLR patients considered for HT. Patients considered for HT + CT have the highest likelihood of a RC based on RS.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. RESULTS: Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. CONCLUSION: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.

BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. METHODS: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

Survival in overweight patients with advanced pancreatic carcinoma: a multicentre cohort study.

BACKGROUND: Obesity is a risk factor for developing pancreatic cancer. We investigated the impact of obesity on survival in patients diagnosed with locally advanced or metastatic pancreatic cancer. METHODS: In a multicentre, retrospective study, we included all patients with advanced or metastatic pancreatic cancer treated at four Swiss hospitals between 1994 and 2004. We categorized patients into four body mass index (BMI) groups (<18.5, 18.5 - 25, ≥ 25 - 29, ≥30 kg/m2) and used multivariable Cox regression to investigate the impact of BMI on survival. Missing data were handled using multiple imputations. RESULTS: 483 patients were included. Median age was 66 years (range 59-74), 47% were female, 82% had stage IV disease, 72% had an ECOG below 2, and 84% were treated with gemcitabine-based first-line chemotherapy. After a median follow-up of 8.5 months, 6 and 12-month survival probabilities of the whole cohort were 67% (95% CI 63% - 71%) and 37% (95% CI 33% - 42%), respectively. Unadjusted 12-month survival rates in each BMI group were: 48% (95% CI 33% - 62%), 42% (95% CI 36% - 48%), 30% (95% CI 22% - 38%), and 11% (95% CI 4% - 24%), respectively. In multivariable analysis, increasing BMI (HR 1.22, 95% CI 1.04 - 1.41, p = 0.012) and CA 19-9 (HR 1.07, 95% CI 1.02 - 1.11, p = 0.003) were significantly associated with worse survival prognosis. Patients with a good clinical performance status (ECOG < 2) had a better prognosis (HR 0.76, 95% CI 0.65 - 0.96, p = 0.019). CONCLUSIONS: Obese patients diagnosed with advanced pancreatic cancers have a worse prognosis compared to non-obese patients. BMI should be considered for risk stratification in future clinical trials.

Cheetahs and wild dogs show contrasting patterns of suppression by lions.

Top predators can dramatically suppress populations of smaller predators, with cascading effects throughout communities, and this pressure is often unquestioningly accepted as a constraint on mesopredator populations. In this study, we reassess whether African lions suppress populations of cheetahs and African wild dogs and examine possible mechanisms for coexistence between these species. Using long-term records from Serengeti National Park, we tested 30 years of population data for evidence of mesopredator suppression, and we examined six years of concurrent radio-telemetry data for evidence of large-scale spatial displacement. The Serengeti lion population nearly tripled between 1966 and 1998; during this time, wild dogs declined but cheetah numbers remained largely unchanged. Prior to their local extinction, wild dogs primarily occupied low lion density areas and apparently abandoned the long-term study area as the lion population 'saturated' the region. In contrast, cheetahs mostly utilized areas of high lion density, and the stability of the cheetah population indicates that neither high levels of lion-inflicted mortality nor behavioural avoidance inflict sufficient demographic consequences to translate into population-level effects. Population data from fenced reserves in southern Africa revealed a similar contrast between wild dogs and cheetahs in their ability to coexist with lions. These findings demonstrate differential responses of subordinate species within the same guild and challenge a widespread perception that lions undermine cheetah conservation efforts. Paired with several recent studies that document fine-scale lion-avoidance by cheetahs, this study further highlights fine-scale spatial avoidance as a possible mechanism for mitigating mesopredator suppression.

In-situ investigation of solid phase evolution during lyophilization of mannitol-based antibody formulations using an XRPD climate chamber.

Crystalline mannitol is commonly used as bulking agent in antibody formulations to provide structure to the lyophilized cake and prevent collapse. Depending on the lyophilization process conditions mannitol can either crystallize as α-, ß-, δ-mannitol, mannitol-hemihydrate, or transition to its amorphous state. While crystalline mannitol helps to create a firmer cake structure this is not true for amorphous mannitol. The hemihydrate is also an undesired physical form as it may reduce the drug product stability by releasing bound water molecules into the cake. Our aim was to simulate lyophilization processes in an X-ray powder diffraction (XRPD) climate chamber. In the climate chamber, the process can be carried out fast with low sample quantities to determine optimal process conditions. Insights on the emergence of desired anhydrous mannitol forms helps to adjust the process parameters in larger scale freeze-dryers. In our study we have identified the critical process steps for our formulations and then varied relevant process parameters, which were the annealing temperature, annealing time and temperature ramp rate of the freeze-drying process. Furthermore, the effect of the presence of antibodies on excipient crystallization was investigated by performing the studies on placebo solutions versus two respective antibody formulations. A comparison of the products obtained in a freeze-dryer and the simulated process in the climate chamber showed good accordance demonstrating the method as suitable tool to identify ideal process conditions on a laboratory scale.

Employment trajectories of young women with breast cancer: an ongoing prospective cohort study in Italy and Switzerland.

PURPOSE: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity. METHODS: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC. Women completed surveys at baseline and every 6 months for 3 years, then yearly for up to 10 years to assess, among other variables, employment status, sociodemographic, medical, and treatment data. Symptoms were assessed by the Breast Cancer Prevention Trial symptom scales and single items from the Cancer Rehabilitation Evaluation System. Univariable and multivariable multinomial logistic regression analyses identified factors associated with changes in employment status. RESULTS: Among the 245 women included in this analysis, 85% were employed at the last individual post-baseline assessment (1 to 10 years). At 5 years, women had a 29.4% probability (95% CI: 23.6-35.5) of experiencing any reduction and a 14.9% probability (95% CI: 10.6-19.9) of experiencing any increase in work activities. Being enrolled in Switzerland (vs. Italy) and reporting more trouble in performing daily activities were significantly associated with work reduction. CONCLUSION: Our results suggest that most young BC survivors remain employed in the long-term. IMPLICATIONS FOR CANCER SURVIVORS: Regular evaluation of symptoms which may interfere with daily life and identification of financial discomfort is critical in providing timely and individually tailored interventions and in limiting unwanted reductions in work activities.

Treatment landscape of metastatic pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a dismal prognosis. The lack of symptoms in the early phase of the disease makes early diagnosis challenging, and about 80-85% of the patients are diagnosed only after the disease is locally advanced or metastatic. The current front-line treatment landscape in local stages comprises surgical resection and adjuvant chemotherapy. In Switzerland, although both FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens are feasible and comparable in the first-line setting, FOLFIRINOX is preferred in the treatment of fit (Eastern Cooperative Oncology Group [ECOG] performance status [PS]: 0-1), young (<65 years old) patients with few comorbidities and normal liver function, while gemcitabine plus nab-paclitaxel is used to treat less fit (ECOG PS: 1-2) and more vulnerable patients. In the second-line setting of advanced PDAC, there is currently only one approved regimen, based on the phase III NAPOLI-1 trial. Furthermore, the use of liposomal-irinotecan in the second line is supported by real-world data. Beyond the standard of care, various alternative treatment modalities are being explored in clinical studies. Immunotherapy has demonstrated only limited benefits until now, and only in cases of high microsatellite instability (MSI-H). However, data on the benefit of poly (ADP-ribose) polymerase (PARP) inhibition as maintenance therapy in patients with germline BRCA-mutated tumors might signal of an advance in targeted therapy. Currently, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions. Thus, identification of predictive and prognostic biomarkers and evaluating novel treatment strategies are equally relevant for improving the prognosis of metastatic pancreatic cancer patients.

Demonstrating Apparently Inconspicuous but Sensitive Impacts on the Rollover Failure of Lithium-Ion Batteries at a High Voltage.

Layered oxides, such as Li[Ni0.5Co0.2Mn0.3]O2 (NCM523), are promising cathode materials for operation at a high voltage, i.e., high-energy lithium-ion batteries. The instability-reasoned transition metal dissolution remains a major challenge, which initiates electrode cross-talk, alteration of the solid electrolyte interphase, and enhanced Li-metal dendrite formation at the graphite anode, consequently leading to rollover failure. In this work, relevant impacts on this failure mechanism are highlighted. For example, a conventional coating of NCM523 with aluminum oxide as a typical high-voltage modification improves kinetic aspects but can only postpone the rollover failure to later charge/discharge cycles. Interestingly, a similar effect on the rollover failure is observed merely after modification of the cell formation protocol, i.e., the first cycles. Further influences of specific test protocols are highlighted and show that the rollover failure even disappears at C-rates above 2C, which can be attributed to a more homogeneous distribution of Li-metal dendrite formation. It is worth noting that a variation of anode porosity can reveal similar effects, as, e.g., variations in anode processing also impact Li dendrite distribution and the appearance of rollover failure. Overall, the rollover failure is a valid but complex phenomenon, which sensitively depends on apparently inconspicuous parameters and should not be disregarded.

Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article.

BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. SUMMARY: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.

Pilot Testing of a Nurse-Led Basic Symptom Self-management Support for Patients Receiving First-Line Systemic Outpatient Anticancer Treatment: A Cluster-Randomized Study (Symptom Navi Pilot Study).

BACKGROUND: The Symptom Navi Program (SNP) is a nurse-led intervention supporting basic symptom self-management for patients with any cancer diagnosis. The SNP has been accepted by patients and healthcare professionals alike. OBJECTIVE: The aims of this study were to pilot the SNP and evaluate patient-reported symptom outcomes, nursing support for symptom management, and patient safety. METHODS: Using a cluster-randomized design, we randomized centers to the intervention (SNP) or control group (usual care). Adult patients starting first-line systemic cancer treatment were included. The primary outcome was the change in symptom interference with daily functions from treatment onset to 16 weeks. Secondary outcomes included changes in symptom severity, symptom burden, self-efficacy, and perceived symptom management support and patient safety. We used linear and logistic mixed-effects models to pilot-test differences in mean changes between groups. The trial was registered with ClinicalTrials.gov (NCT03649984). RESULTS: Changes in symptom interference with daily functions did not differ (mean difference at 16 weeks: -0.50; 95% confidence interval, -1.38 to 0.38; P = 0.25) between SNP (3 centers, 49 patients) and control (5 centers, 85 patients) as for all other outcomes. No adverse events were reported. CONCLUSIONS: Our preliminary findings did not indicate an effect of the SNP on patient-reported symptom outcomes, self-efficacy, or symptom management support. Inadequate power and SNP components (eg, insufficient training, low number of follow-up consultations) may be attributed to the lack of an observed effect. IMPLICATIONS FOR PRACTICE: The SNP training content and intervention procedures merit reconsideration.

Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study.

BACKGROUND AND AIM: It is unknown whether sorafenib can be combined with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma. This study assesses the safety and tolerability of a continuous regimen of sorafenib combined with TACE. METHODS: This was an open-label phase I study testing a continuous administration of sorafenib (dose escalation from 200 mg twice daily [bid] to 400 mg bid) starting 7 days prior to TACE with doxorubicin (50 mg). RESULTS: Twenty-one patients were screened and 14 received sorafenib combined with TACE. Because there were no dose-limiting toxicities in the first three patients who received sorafenib at a dose of 200 mg bid, subsequent patients received 400 mg bid. Twenty-seven procedures were performed (median, two per patient) and two local therapy-related severe adverse events occurred. The median duration of sorafenib therapy was 246 days (range, 14-547 days). Sorafenib-related adverse events of grade ≥3 were hand-foot skin reaction (n = 3), weight loss (n = 2), diarrhea (n = 1), abdominal pain (n = 1), and thrombocytopenia (n = 3). After treatment with sorafenib and TACE, there was a significant decrease in the concentration of plasma vascular endothelial growth factor (VEGF) from 93 ng/l to 67 ng/l. CONCLUSIONS: Continuous administration of sorafenib at a dose of 400 mg bid combined with TACE was tolerable. The adverse event profile of this regimen was comparable with that of sorafenib monotherapy with the exception of thrombocytopenia, which may be more frequent. There were no increases in the circulating VEGF levels after TACE with this combined regimen. (Swiss Association for the Study of the Liver study number 25; ClinicalTrials.gov trial identifier, NCT00478374).

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Intense therapy in patients with locally advanced esophageal cancer beyond hope for surgical cure: a prospective, multicenter phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02).

BACKGROUND: There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option. PATIENTS AND METHODS: Patients with cervical esophageal tumors, locally very advanced stage (T4 and/or M1a) or locally advanced (T3 and/or N+) with comorbidities were included. THERAPY: 2 cycles of induction chemotherapy (cisplatin and docetaxel, both 75 mg/m(2) 3-weekly) followed by chemoradiation therapy (CRT) comprising a total radiation dose of 59.4 Gy together with docetaxel 15 mg/m(2) and cisplatin 25 mg/m(2) (5 weekly doses). Primary endpoint: Histologically proven freedom from local failure 6 months after CRT completion. RESULTS: 21 patients were included: 12 had locally very advanced tumors, 3 had cervical esophagus tumors, and 6 were medically unfit for surgery. 18 patients completed therapy per protocol. Grade 3/4 toxicities during CRT were thrombopenia (10%) and dysphagia (15%). 1 patient died due to herpes simplex infection. The primary endpoint was achieved by 4 patients, 6 were alive after median follow-up of 34 months, and median survival was 16 months. Most patients experienced lasting improvement of dysphagia following induction chemotherapy. CONCLUSIONS: This regimen is feasible, showed clinically meaningful, long-lasting improvements in quality of life and resulted in long-term survival in 29% of the patients.

Metastatic Colorectal Carcinoma after Second Progression and the Role of Trifluridine-Tipiracil (TAS-102) in Switzerland.

BACKGROUND: Metastatic colorectal carcinoma (mCRC) is one of the most prevalent types of cancer worldwide. After tumor progression with first- and second-line treatment, trifluridine (FTD) and tipiracil (TPI) has been shown to be a treatment option. SUMMARY: Data from a pivotal phase 3 trial (RECOURSE) and an ongoing phase 3b trial (PRECONNECT) have shown that, in mCRC patients who experienced disease progression after 2 lines of standard therapy, treatment with FTD/TPI is safe and efficacious. Other third-line options include regorafenib, rechallenge with previous treatment lines or personalized approaches based on comprehensive molecular profiling. Randomized trials or sequential studies aiming for the right treatment sequence or predefined subtypes for FTD/TPI or regorafenib as well for rechallenge are missing. However, FTD/TPI as well as regorafenib are recommended by the current ESMO, German S3, and National Comprehensive Cancer Network (NCCN) guidelines in the same situation, thus offering physicians a number of alternatives for the treatment of mCRC patients after the second progression. Key Message: This narrative review summarizes published data and their impact for FTD/TPI as well for regorafenib and rechallenge chemotherapy in clinical practice settings of refractory situations of colorectal cancer.

European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment.

BACKGROUND: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. METHODS: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. RESULTS: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)-39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. CONCLUSION: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.