The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Effect of Collaborative Review of Electronic Patient-Reported Outcomes for Shared Reporting in Breast Cancer Patients: Descriptive Comparative Study.

BACKGROUND: Digital monitoring of treatment-related symptoms and self-reported patient outcomes is important for the quality of care among cancer patients. As mobile devices are ubiquitous nowadays, the collection of electronic patient-reported outcomes (ePROs) is gaining momentum. So far, data are lacking on the modalities that contribute to the quantity and quality of ePROs. OBJECTIVE: The objective of our study was to compare the utilization of two versions of a subsequently employed mobile app for electronic monitoring of PROs and to test our hypothesis that a shared review of symptoms in patient-physician collaboration has an impact on the number of data entries. METHODS: The Consilium Care app engages cancer patients to standardize reporting of well-being and treatment-related symptoms in outpatient settings. For descriptive comparison of the utilization of two slightly different app versions, data were obtained from an early breast cancer trial (version 1 of the app, n=86) and an ongoing study including patients with advanced disease (version 2 of the app, n=106). In both app versions, patients and doctors were allowed to share the information from data entries during consultations. Version 2 of the app, however, randomly selected symptoms that required a detailed and shared regular patient-doctor review in order to focus on the collection and appropriate interpretation regarding awareness and guidance for severity grading. The numbers and types of symptom entries, satisfaction with both app versions, and patients' perceived effects during consultations were included for analysis. RESULTS: Symptom severity grading was performed according to the Common Terminology Criteria for Adverse Events (CTCAE) using a horizontal slider and was indicated in descriptive terminology in both apps, while a graphical display facilitated the illustration of symptom history charts. In total, 192 patients electronically reported 11,437 data entries on well-being and 33,380 data entries on individual symptoms. Overall, 628 (of 872 intended) requested patient-doctor symptom reviews were performed in version 2 of the app. Both the amount of data entries per patient and day for well-being (version 1 vs version 2: 0.3 vs 1.0; P<.001) and symptoms (version 1 vs version 2: 1.3 vs 1.9; P=.04) appeared significantly increased in version 2 of the app. Overall satisfaction with both app versions was high, although version 2 of the app was perceived to be more helpful in general. CONCLUSIONS: Version 2 of the app showed much better results than version 1 of the app. A request for collaborative patient-doctor symptom review is likely to affect the number of digital symptom data entries. This app shows high potential to improve the patient-doctor experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT02004496; https://clinicaltrials.gov/ct2/show/NCT02004496 and ClinicalTrials.gov NCT03578731; https://clinicaltrials.gov/ct2/show/NCT03578731.

Quality of life and pain in patients with metastatic bone disease from solid tumors treated with bone-targeted agents- a real-world cross-sectional study from Switzerland (SAKK 95/16).

BACKGROUND: Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors. Knowledge of the impact of their routine care use on patient-reported pain and bone pain-related quality of life (QoL) is limited. METHODS: This real world, cross-sectional study enrolled patients over a 3-month period through oncologists across Switzerland. Patients were ≥ 18 years, had solid tumors and at least one bone metastasis, and received routine care for bone metastases. Physicians provided data on BTA-related practices, risk of bone complications and BTA regimen. Patients completed questionnaires about pain (BPI-SF), general and bone pain-related QoL (FACT-G, FACT-BP) and treatment satisfaction (FACIT-TS-G). RESULTS: Eighteen sites recruited 417 patients. Based on the FACT-BP, 42% of the patients indicated not having bone pain. According to the BPI-SF, 28% reported no, 43% mild, 14% moderate, and 15% severe pain, respectively. Patients not treated with a BTA had better overall QoL (FACT-G: p = 0.031) and bone pain-related QoL (FACT-BP, p = 0.007) than those treated with a BTA. All pain and other QoL scales did not differ between groups. Patients perceived at 'low risk of bone complications' by their physician not receiving a BTA reported less pain and better QoL than those considered at 'low risk' but receiving BTA treatment or those considered at 'high risk' regardless of BTA treatment. Overall satisfaction with the treatment was good; almost 50% of patients reporting that they were completely satisfied. CONCLUSIONS: Overall, pain and QoL did not differ according to BTA treatment or physicians' risk perception. Patient with low risks not receiving BTA treatment reported least pain and highest QoL scores. These results may suggest that treating physicians assess bone complication risk appropriately and treat patients accordingly, but they need to be confirmed by objective determination of longitudinal skeletal complication risk.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Patterns of care for patients with metastatic bone disease in solid tumors: A cross-sectional study from Switzerland (SAKK 95/16).

BACKGROUND: Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors, but knowledge of their routine care use and the therapeutic implications remains limited. This non-interventional study aimed to characterize real-world BTA patterns of care in Switzerland. MATERIALS AND METHODS: Non-interventional, cross-sectional study involving oncologists from across Switzerland who completed a Treating Physician questionnaire, providing data on their clinical setting and BTA-related practices, and a Patient Characteristics and Treatment questionnaire, providing data on their patients' disease status, risk of bone complications, BTA regimen and related outcomes. Eligible patients were aged ≥ 18 years, with solid tumors and at least one bone metastasis and were receiving routine management at the participating physician's center over the 3-month study period. RESULTS: A total of 86 oncologists recruited 417 patients from across 18 centers in Switzerland (80% public hospitals; 20% private clinics). The majority of physicians (70.9%) reported prescribing BTAs in line with international guidelines; denosumab was the treatment of choice in 78.5% of patients. BTAs were widely administered (94.2%) according to a 3-4-weekly dosing regimen; 33.7% of physicians reported extending intervals to 12 weeks after an initial 2 years of treatment. Physicians appeared to use clinical judgement, as well as formal risk assessment, to guide treatment for symptomatic skeletal events. No association was seen between either BTA use, or risk of complications, and incidence of skeletal complications. Only 4.3% of patients were reported to be experiencing severe bone pain at the time of the study. CONCLUSIONS: This cross-sectional, non-interventional study found high implementation of guideline-recommended BTA prescribing, good pain control and low incidence of skeletal-related events. Long-term BTA randomized controlled trials have the potential to further optimize routine care outcomes for patients.

Impact of Time to Start Systemic Therapy on the Outcomes of Patients with Metastatic Colorectal Cancer Treated with First Line FOLFOX Chemotherapy; a Patient-Level Pooled Analysis of Two Clinical Trials.

BACKGROUND: Impact of time to start first-line systemic chemotherapy following diagnosis of metastatic colorectal cancer (mCRC) needs to be studied. METHODS: This is a pooled analysis of the raw data of the comparator arms of two randomized studies (NCT00272051; NCT00305188). Univariate and multivariate analyses of predictors of overall and progression-free survival were conducted through Cox regression analysis. Factors with statistically significant P value (P < 0.05) in the univariate part of the analysis were included in the multivariate analysis. RESULTS: In univariate analysis, time to start systemic therapy did not affect overall or progression-free survival (P=0.694; P= 0.891 respectively). In multivariate analysis for overall survival, the following factors were predictive of worse overall survival: younger age (P = 0.019), higher ECOG performance score (P = 0.001), more than one site of metastatic disease (P = 0.002), colon site of the primary tumor (P = 0.004), and no oncologic surgery to the primary tumor (P < 0.001). Likewise, in multivariate analysis for progression-free survival, the following factors were predictive of worse progression-free survival: no oncologic surgery to the primary (P < 0.001), more than one organ of metastatic disease (P < 0.001), and no concurrent bevacizumab administration (P = 0.015). CONCLUSION: Time to start systemic chemotherapy does not appear to impact overall or progression-free survival among mCRC patients.

Impact of primary tumor side on the outcomes of patients with non-metastatic colon cancer; a patient-level pooled analysis of two clinical trials.

OBJECTIVE: To assess the impact of primary tumor side on the outcomes of non-metastatic colon cancer patients included in two clinical trials. METHODS: Overall and disease-free survivals were assessed according to the side of the tumor, through Kaplan-Meier analysis. Univariate and Multivariate analysis of predictors of disease-free survival was performed through Cox regression analysis. RESULTS: Kaplan-Meier analysis of disease-free survival according to the side of the primary tumor was conducted. In the overall cohort, the right-sided disease has longer disease-free survival compared to left-sided disease (p = 0.005). When the analysis was repeated among different treatment strata (observation, adjuvant 5FU/LCV, adjuvant edrecolomab), right-sided colon cancer has longer disease-free survival among observation-treated patients only (p = 0.020). Multivariate analysis was conducted among the three subsets of adjuvant treatment. The left side of the primary tumor was predictive of worse disease-free survival in patients treated with observation only (p = 0.005) but not in patients treated with adjuvant 5FU/LCV (p = 0.345) or patients treated with adjuvant edrecolomab (p = 0.661). CONCLUSION: Stage II right-sided colon cancer patients have better disease-free survival compared to stage II left-sided colon cancer patients when treated with surgery only. This survival difference disappears if patients were treated with adjuvant fluoropyrimidines.

Assessment of the external validity of the American Joint Committee on Cancer 8th staging system for anal carcinoma.

BACKGROUND: The current study evaluates the prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for patients with anal carcinoma. PATIENTS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database (2004-2014) was explored and AJCC 6th and 8th stages were formulated. Through Kaplan-Meier analysis, overall survival analyses were performed. The Cox regression model (adjusted for age, gender, histology, ethnicity, subsite and grade) was calculated for cancer-specific survival and, subsequently, pairwise comparisons of hazard ratios were calculated. RESULTS: A total of 11,934 anal carcinoma patients were included in the analysis. Overall survival was compared according to both AJCC 6th and 8th systems. For both staging systems, the p value for the trend in overall survival was significant (p < .0001). Nevertheless, for the AJCC 6th system, stage IIIA and IIIB curves were overlapping; while for the AJCC 8th system, the median survival for stage IIB was lower than the mean survival for stage IIIA (74 months vs. 96 months). Moreover, stage IIIB and stage IIIC curves were overlapping. The cause-specific (cancer-specific) Cox regression hazard was calculated for both staging systems. Pairwise hazard ratio comparisons between different AJCC 6th stages were performed and all p values for comparisons were significant (p < .05). Pairwise hazard ratio comparisons between different AJCC 8th stages were performed and only the following comparisons were significant (p < .0001) (I vs. IIA; IIA vs. IIB; IIIC vs. IV). The C-statistic (using death from anal carcinoma as the dependent variable) for the AJCC 6th staging system was: 0.681 (SE: 0.009; 95% CI: 0.664-0.698); while the C-statistic for the AJCC 8th staging system was 0.687 (SE: 0.008; 95% CI: 0.670-0.703). CONCLUSIONS: There is no evidence of significant improvement in the AJCC 8th edition compared to AJCC 6th (or 7th) edition in terms of overall or cancer-specific survival prediction.

Exploring the differences between early-onset gastric cancer and traditional-onset gastric cancer.

BACKGROUND: The current study sought to explore the potential clinical, epidemiological and genetic differences between early-onset gastric cancer (E-gastric cancer: defined as 20-39 years) and traditional-onset gastric cancer (T-gastric cancer: defined as ≥40 years). METHODS: Datasets from the following sources were searched: Surveillance, Epidemiology and End Results database [2000-2014], Behavioral Risk Factor Surveillance Survey and the cancer genome atlas (TCGA). Clinicopathological characteristics, trends, and genetic findings were compared between E-gastric cancer and T-gastric cancer. Moreover, correlations with relevant risk factors were sought after. RESULTS: A total of 95,323 gastric cancer patients were identified in the period from 2000 to 2014. While T-gastric cancer was decreasing during the study period (-1.4; P<0.05), E-gastric cancer was stable during the study period. E-gastric cancer is less prevalent in males (51.1% vs. 61.0%; P<0.0001), and white patients (68.9% vs. 71.4%; P<0.0001). E-gastric cancer patients usually present with poorly differentiated histology (55.3% vs. 48.0%; P<0.0001) as well as more aggressive histological subtypes (e.g., diffuse histology or linitis plastica). No difference can be detected with regards to risk factor correlations between E-gastric cancer and T-gastric cancer. Only four patients with E-gastric cancer were available in the provisional TCGA dataset at the time of the study. CONCLUSIONS: E-gastric cancer is a potentially distinct disease entity with specific clinicopathological and trend patterns compared to conventional T-gastric cancer. Further studies are needed to explore the potential etiologic basis as well as to investigate the clinical consequences of this distinction. The impact of this distinction on minority populations requires further assessment as well.

Early stage hepatocellular carcinoma in the elderly: A SEER database analysis.

BACKGROUND: Scarce evidence exists regarding the management of elderly patients (≥70years) with hepatocellular carcinoma (HCC). This study assessed the presentation and outcomes of elderly patients with early stage HCC. METHODS: Patient with early stage HCC (T1/T2N0M0), ≥70years, diagnosed between 2004 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity score matching (for receipt of localized treatment) was performed considering baseline characteristics (age, gender, race, tumor (T) stage, tumor size, fibrosis score, alpha fetoprotein level and histological subtype). RESULTS: A total of 6693 patients were identified. The median age group was 75-80years, and 2457 patients received local treatment (either surgical or non-surgical treatment). Both before and after propensity score matching, cancer-specific and overall survival (P<0.0001 for all) were better in the local treatment group. When stratifying the overall survival according to age group (70-80years vs. >80years) in the post matching cohort, patients treated with local treatment have better overall survival than those not treated regardless of the age group (P<0.0001 for both groups). In multivariate analysis of the matched population: local treatment, normal AFP and age (70-80years) were associated with better overall survival (P<0.0001, P<0.0001, P=0.047; respectively). CONCLUSION: Within the known limitations of the current SEER analysis, it may be cautiously suggested that elderly patients with early HCC should be properly selected for potentially curative local therapies. Prospective confirmation of these results should be conducted.

Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review.

INTRODUCTION: Immune-related ocular toxicities are uncommon but serious adverse events that may be associated with the use of immune checkpoint inhibitors. The objective of this review is to assess the incidence and risk of ocular toxicities which are potentially immune-related and occur with immune checkpoint treatment of solid tumors. Areas covered: PubMed database has been searched till June 2016. Prospective clinical trials reporting the occurrence of immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors were included. Eleven trials with 4965 participants were included. These studies included one study for ipilimumab and tremelimumab, three studies for nivolumab, five studies for pembrolizumab and one study comparing pembrolizumab to ipilimumab. No atezolizumab studies were included. The most common ocular toxicities reported with these agents included uveitis and dry eyes. Pooled analysis for odds ratio of all-grade immune-related ocular toxicities is 3.40 [95% CI: 1.32-8.71; P = 0.01]. Expert commentary: Despite being uncommon, immune-related ocular toxicities (particularly uveitis and dry eyes) occur with a higher frequency in cancer patients treated immune checkpoint inhibitors compared to those treated with control regimens.

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis.

AIM: To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. METHODS: SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. RESULTS: A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival. CONCLUSION: Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.