•No standard of care exists for L2 treatment after L1 chemo-immunotherapy in NSCLC.•Platinum rechallenge and taxane + antiangiogenic are valuable regimens in this setting.•Patients resistant to L1 ...treatment (PFS < 6mo) have poorer outcomes in L2.•Patients with high PD-L1 expressing tumors had better outcomes in L2.
Chemotherapy plus immunotherapy is the standard of care for patients with metastatic NSCLC. No study has evaluated the outcomes of second-line chemotherapy treatments after progression following first-line chemo-immunotherapy.
This multicenter retrospective study evaluated the efficacy of second line (2L) chemotherapies after progression under first-line (1L) chemo-immunotherapy, measured by overall survival (2L-OS) and progression free survival (2L-PFS).
A total of 124 patients were included. The mean age was 63.1 years, 30.6 % of the patients were female, 72.6 % had an adenocarcinoma and 43.5 % had a poor ECOG-performance status prior to 2L initiation. Sixty-four (52.0 %) patients were considered resistant to first line chemo-immunotherapy. (1L-PFS < 6 months). In 2L treatments, 57 (46.0 %) patients received taxane monotherapy, 25 (20.1 %) taxane plus anti-angiogenic, 12 (9.7 %) platinum-based chemotherapy and 30 (24.2 %) other chemotherapy.
At a median follow-up of 8.3 months (95 %CI: 7.2–10.2), post initiation of 2L treatment, the median 2L-OS was 8.1 months (95 % CI: 6.4–12.7) and the median 2L-PFS was 2.9 months (95 %CI: 2.4–3.3). Overall, the 2L-objective response and 2L-disease control rates were 16.0 %, and 42.5 %, respectively.
Taxane plus anti-angiogenic and platinum rechallenge achieved longest median 2L-OS: not reached (95 %CI: 5.8-NR) and 17.6 months (95 %CI 11.6-NR), respectively (p = 0.05).
Patients resistant to the 1L treatment had inferior outcomes (2L-OS 5.1 months, 2L-PFS 2.3 months) compared with 1L responders (2L-OS 12.7 months, 2L-PFS 3.2 months).
In this real-life cohort, 2L chemotherapy achieved modest activity following progression under chemo-immunotherapy. 1L-resistant patients remained a refractory population, highlighting a need for new 2L strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Background: Optimal comprehensive survivorship care, beyond screening of recurrences and new cancers, and including health promotion, management of physical as well as psychosocial needs and ...chronic conditions is insufficiently delivered. To increase patient (pt) empowerment and maximize the uptake of multidisciplinary strategies serving all survivorship needs, we implemented a proactive survivorship care pathway offered for pts with early BC at the end of their primary treatment phase (surgery, chemotherapy, radiotherapy). Methods: The pathway consisted of the following components: 1) receipt of a personalized survivorship care plan (SCP), 2) invitation to attend face-to-face group seminars focused on specific themes and a comprehensive survivorship consultation for multidisciplinary referrals (”the transition day”) 3) access to a mobile application (app) delivering personalized education according to symptoms reported and 4) decision aids for helping physicians to manage prevalent symptoms and side effects related to BC treatment. Administrative data were collected. A pre-specified post-experience survey was sent to all pts four weeks post pathway delivery to inform program implementation with a minimum requirement of 50 responses. BC physicians and members of the multidisciplinary implementation team (MIT) answered a dedicated survey. For the overall pathway and each of its components we descriptively evaluated the following domains: satisfaction (primary outcome), uptake, perceived usefulness, barriers for delivery, and suggestions for improvement. A 70% satisfaction rate would define a positive experience. Results: From October 2021 to April 2022, 241 SCP were delivered, and 98 pts attended the “transition day”. 62 pts replied to the survey, 42 (67%) had received the SCP, 34 (55%) attended the “transition day”, 36 (57%) accessed the app. Only 21 pts (34%) who answered the survey received the full pathway, 81% of whom were very or completely satisfied with it. Perceived usefulness of individual components and for pts that received the full pathway were, respectively: 64% and 90% for the SCP, 91% and 95% for the “transition day”, 72% and 90% for the app. Among 14 BC physicians, agreement regarding the usefulness of the components was: 93% for the SCP, 86% for the decision aids, 93% for the “transition day”, and 86% for the app. The MIT (n = 13) reported high engagement and satisfaction (100%). Main actionable points for improvement included: automated screening and SCP preparation, virtual “transition day”, increase physicians’ awareness. Conclusions: In this pilot phase, pts were satisfied with receiving a proactive survivorship care pathway and the majority reported that the components were useful for supporting their needs. This study informed improvements on program penetration. Evolution towards sustainability phase is ongoing including dissemination to other cancers and centers.
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Background: Upfront Immune Checkpoint Blockers (ICB) alone or in combination with chemotherapy (CT) have become the backbone treatment of non-oncogene addicted aNSCLC. PD-L1 remains the only ...predictive biomarker, but additional biomarkers are mandatory to better discriminate the population more suitable for the combination approach (CT-ICB). We hypothesized that TLG, a parameter that measure tumor burden and metabolic activity, may help to select the optimal first-line regimen. Methods: We performed a multicentric (n = 5) retrospective study including pts treated either with ICB alone, CT-ICB or CT alone. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional Hazard models adjusting for relevant covariates (neutrophil/lymphocyte ratio, ECOG PS, liver, bone metastases). TLG was calculated on PET scans as the product of metabolic tumor volume (with a threshold of 42% of SUV max) and SUV mean. Results: 250 pts with aNSCLC initiated first-line treatment (94 ICB, 102 CT-ICB and an hystorical control group of 54 CT) within 42 days from PET. Median follow up was 22 months for ICB, 16 for CT-ICB and 47 for CT. 170 pts were male (68%), 210 had non-squamous histology (84%), 110 (44%)and 38 (15%) had bone and liver metastasis, respectively. On the 194 pts with PD-L1 status available: 20%, 29% and 50% had PD-L1 < 1%, 1-49% and > 50%, respectively. No correlation was seen between PD-L1 and TLG. Presence of liver metastases (13% vs 2%) and ECOG PS > 1 (16% vs 3%) were associated with elevated TLG. PFS correlated with TLG, with longer median PFS in the lower quartile (TLG < 380) either with ICB (12.4 vs 4.7 months, HR 1.9, 95% CI1.1 – 3.35, p 0.025) and CT-ICB (17.9 vs 7.3, HR 1.9, 95% CI1.1 – 3.7, p 0.032) but not with CT (4.2 vs 3.5, p 0.986), whereas OS was correlated with TLG < 380 in all 3 groups. The risk of progression under ICB was lower in tumors with TLG < 380 (15% vs.29%, p = 0.02), but no difference was seen in other 2 groups. In PD-L1 ≥50% pts with elevated TLG, treatment with CT-ICB (n = 20) increased the PFS respect with ICB (n = 55) (10.7 vs 3.9, HR 0.54, 95% CI 0.29 – 0.99, p = 0.048).The analysis was underpowered to find a difference in OS (HR 0.49, 95% CI 0.21 - 1.12, p = 0.092). Conclusions: TLG retains a prognostic validity in aNSCLC identifying pts with an increased rate of early progression on ICB, who may benefit from CT-ICB. Further analyses are required to compare CT-ICB and ICB in PD-L1 ≥50% according to TLG. Enrollement from other centers is ongoing, an update will be presented.
Abstract
Background: We previously developed a clinico-behavioral model of CRF and reported an increased risk of severe CRF among survivors of breast cancer (BC) receiving adjuvant hormonal therapy ...(HT) (Di Meglio A, ASCO 2021). We now aim to comprehensively explore the contribution of relevant serum proteins in explaining CRF. We adopted a multimodal approach, both (1) hypothesis-driven, based on the rationale that deregulation of systemic inflammatory processes and mediators of immunologic or neuroendocrine activation are associated with vulnerability to CRF, and (2) discovery-driven, based on proteomic analyses. Methods: Women with stage I-III HR+/HER2- tumors receiving HT (N=1153) were included from the multicenter, prospective CANTO cohort (NCT01993498). The primary outcome of interest was severe post-treatment global CRF at year-2 (Y2) after diagnosis (score ≥ 40/100, EORTC QLQ-C30). Secondary outcomes included CRF dimensions (physical, emotional, cognitive; EORTC QLQ-FA12). For the hypothesis-driven analyses, pre-treatment blood samples were profiled (Randox Laboratories Limited, UK) at diagnosis of BC, using a multi-biomarker panel assessing IL6, TNFα, IL1RA, CRP, IL2, IL1β, IFNγ, IL10, IL1A, IL4, and IL8. Pre-specified pre-treatment clinico-behavioral covariates (age, BMI, smoking status, psychological, and pre-treatment symptom burden, based on previously developed models) were forced into a multivariable logistic regression. Biomarkers were retained by Augmented Backwards Elimination (p<0.05) only if significantly associated with CRF. For the discovery approach, we used hyper-reaction monitoring mass spectrometry for the unbiased quantification of all detectable peptides and proteins in human plasma samples at diagnosis (Biognosys, CH), among a discovery subset (N=462). We then aimed to identify a proteomic signature associated with severe CRF at Y2. Log-transformed protein intensities were analyzed in terms of differential expression. The proteins that were identified to be significantly different among the patients reporting and not reporting severe CRF were then used to train a logistic regression model. Results: Prevalence of severe global CRF increased from 21.6% at diagnosis to 34.8% at Y2. In the final model, higher pre-treatment levels of IL6 and lower levels of IFNγ and IL10 were significant predictors of severe global CRF at Y2 (Table). The AUC of this clinico-bio-behavioral model was 0.78 (95%CI 0.75 - 0.82) and was suggestive of an improved performance as compared to clinico-behavioral models. Among CRF dimensions, a significant association emerged only between CRP and severe cognitive CRF (outcome prevalence at Y2 14.2%; adjusted OR per CRP log-unit increase 1.40 95%CI 1.01-1.93).
In the discovery subset, several proteins were identified as differentially regulated (p<0.05) among patients reporting and not reporting severe CRF at Y2. Most of these were related to coagulation pathways (including C4BPA, C4BPB, HABP2, PLF4, PROS). However, models incorporating proteomic data did not seem to augment the predictive ability compared to clinico-behavioral models. Conclusions: Using clinical and biological pre-treatment measurements, it may be possible to identify a subset of BC patients at high risk for increased post-treatment CRF while on HT. This provides the possibility of testing dedicated preventive interventions.
Table. Clinico-bio-behavioral model of pre-treatment predictors of severe global CRF at Y2, incorporating circulating inflammatory biomarkers.Adjusted OR§ (95% CI)Age, per additional 1 year0.98 (0.96-0.99)BMI, per additional unit1.02 (0.99-1.06)Current smoker, vs never2.27 (1.47-3.51)Former smoker, vs never0.97 (0.64-1.46)Anxiety case*, vs normal1.13 (0.75-1.70)Doubtful anxiety*, vs normal1.11 (0.73-1.68)Pre-treatment Insomnia**, per additional 10 points1.09 (1.04-1.15)Pre-treatment Pain**, per additional 10 points1.10 (1.01-1.18)Severe pre-treatment CRF**, vs no4.70 (3.13-7.05)IL6***1.72 (1.25-2.36)IL1RA***1.24 (0.85-1.81)IL2***1.43 (0.99-2.08)IFNγ***0.54 (0.30-0.95)IL10***0.40 (0.18-0.87)IL4***1.47 (0.67-3.20)IL8***1.15 (0.83-1.60)OR= Odds Ratio; CI= Confidence Interval; §by all factors in Table; *HADS; **QLQ-C30; ***per log-unit increase
Citation Format: Antonio Di Meglio, Stergios Christodoulidis, Davide Soldato, Antonin Della Noce, Daniele Presti, Julie Havas, Florine Dubuisson, Barbara Pistilli, Valerie Camara-Clayette, Cecile Charles, Patricia A Ganz, Julienne Bower, Ann H Partridge, Alexandra Jacquet, Sibille Everhard, Sandrine Boyault, Fabrice André, Paul-Henry Cournede, Stefan Michiels, Caroline Pradon, Ines Vaz-Luis. Development of a clinico-bio-behavioral model for cancer-related fatigue (CRF) incorporating inflammatory biomarkers and proteomic data abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-01.
Abstract
Background: Mobile health (mHealth) applications (app) and remote monitoring demonstrated tangible value in terms of improving dose delivery, quality of life and mitigating the severity of ...acute treatment-related side effects, both in the metastatic setting and during the active phase of treatment in patients (pts) with early-stage solid tumors. However, the value of mHealth in ‘after primary treatment’ survivorship phase is less studied. Most BC pts have hormone receptor-positive disease and are eligible for adjuvant ET for 5-10 years. ET is associated with multiple side effects that negatively impact quality of life and treatment adherence. A prior survey among French survivors suggested that pts are willing to use digital companion app to help them in the after-cancer experience. In this setting, we developed a digital companion for survivors of BC receiving ET. Objectives: In this study, we explored acceptability, representations, levers, and barriers to a multimodal mHealth intervention among BC pts treated with ET. Methods: This was a qualitative study based on 3 focus groups (FG) with survivors of BC receiving adjuvant ET. The multimodal mHealth intervention had the following features: measure (symptom reporting), understand, and appease (information on interventions to relieve the symptom). FG were conducted via videoconference, lasted approximately 60-90 min, were recorded and transcribed for analysis. A content, thematic analysis was performed. All participants provided oral informed consent and socio-demographic information. Results: 17 BC survivors from diverse professional and socio-economic background participated. Mean age was 48.5 years (range: 32-61). There was a consensus regarding the acceptability and perception of usefulness of an app during treatment with adjuvant ET. A feeling of loneliness during this period was also expressed. Emergent themes cited included: a) positive representations i) satisfaction with the educational support with language and the level of information of the app judged as appropriate and reliable; ii) hope in the role of the app as a companion to alleviate the loneliness; iii) vehicle to enhance family interaction; iv) tool to boost engagement towards their treatment. b) concerns associated with i) fear of human contact replacement ii) fear of loss of interest over time, particularly in the setting of a 5-10 year journey. Pts were pro-active in providing feedback regarding innovative features that could be integrated: i) including interest on the use of biosensors (step counting, nutritional tracking); ii) to receive personalized encouragement messages and iii) updated information regarding scientific advances related to the treatment of early breast cancer. Most participants found the app to be aesthetically pleasing and easy to use. Conclusions: Findings from this qualitative study are promising regarding the acceptability and perception of usefulness of a personalized app for the mitigation of ET side effects in the adjuvant setting. It highlights the need of personalized educational material, but also maintenance of ‘bi-directional’ communication with health professionals. Optimization of the tool is ongoing and updated FG results will be presented. This tool will be tested in a randomized controlled trial starting in Q1/2022, which will evaluate its effectiveness.
Quotes from participantsThemes emergedParticipants’ quotes from focus groupsSatisfaction with educational support‘’Today we find everything on the internet, bad and good things, we cannot know what is true and what is fake. (⋯) If an app can give us reliable information, good, summarized information, this would be great!’’Satisfaction with educational support; Hope in the role of the app to alleviate loneliness“I didn’t even know we had so many side-effects linked to endocrine therapy. Now I understand that it’s true, it’s not something from my head. It’s related to the treatment and it’s really nice to have this support.”Alleviation of loneliness‘’I often feel lonely, sometimes is difficult to have contact with the doctor.’’, ‘’We feel lonely, even our family cannot understand.’’Alleviation of loneliness‘’We need to exchange with people that lived the same situation.’’, “We go to forums, chats, Instagram⋯”, ‘’We realize that we are not alone, that we are not the only ones with the symptoms.’’Fear of human contact replacement‘’It is a good addition, but it will never replace the relationship that we have with our doctor.’’Fear of loss of interest over time‘’It is a good app to start endocrine therapy⋯ How to make the app interesting and useful during several years of treatment?’’
Citation Format: Elise Martin, Antonio Di Meglio, Pietro Lapidari, Daniele Presti, Davide Soldato, Léna Degousee, Marion Aupomerol, Barbara Pistilli, Léonor Fasse, Diane Boinon, Florian Scotte, Gwenn Menvielle, Agnès Dumas, Céline Lazorthes, Jonathan Benhamou, Matthieu Pozza, Raphaëlle Martin-Neuville, Nicolas Helleringer, Jeanne Eelkema, Fabrice Andre, Ines Vaz-Luis, Maria Alice Franzoi. A multimodal and personalized digital companion to help survivors of breast cancer (BC) manage side effects of adjuvant endocrine therapy (ET): A qualitative exploration abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-27.
Abstract
Background: Up to 35% BC survivors who receive adjuvant treatment (tx) experience severe CRCI, which has a significant impact on quality of life, disrupting daily functioning as well as ...self-esteem, self-confidence, and work ability. However, limited tools exist to predict the risk of CRCI. We aimed to develop a comprehensive model of severe CRCI, including clinical and serum inflammatory protein data. Methods: We included 8875 patients (pts) with stage I-III BC from the multicenter, prospective CANTO cohort (NCT01993498). Longitudinal data were collected at diagnosis (dx), 1 (T1), 2 (T2) and 4 (T3) years post-dx. Our outcome of interest was severe cognitive impairment at T1, T2, and T3 (score < 75/100, EORTC QLQ-C30, Giesinger JM 2020). Multivariable logistic regression models retained associations between baseline clinical variables (sociodemographic, psychological, tumor, and tx-related) with severe CRCI by bootstrapped Augmented Backwards Elimination (ABE). Among a subset of patients with HR+/HER2- BC (N= 1151), blood samples were profiled at dx using a multi-biomarker inflammatory panel assessing IL6, TNFα, IL1RA, CRP, IL2, IL1β, IFNγ, IL10, IL1A, IL4, IL8, and monocyte chemoattractant protein-1 (MCP-1). All biomarkers were incorporated simultaneously into a model of severe CRCI and retained only if significantly associated with CRCI by ABE (p<0.05). Previously retained clinical associations were forced into the model. Results: In the overall cohort, mean age at dx was 56.7 years (SD 11.3), and 52.7% and 81.3% of pts received chemotherapy and hormonal therapy, respectively. Prevalence rates of severe CRCI were 31.2% (dx), 31.4% (T1), 30.9% (T2), and 29.9% (T3). Severe post-tx CRCI was consistently associated with severe pre-tx pain and severe pre-tx CRCI. Severe pre-tx fatigue, younger age, anxiety symptoms and hot flashes at dx were also associated with increased odds of severe CRCI at some post-dx time-points (Table 1). Models Area Under the Curve (AUC) were 0.73 (95% confidence intervals CI 0.70-0.76) at T1, 0.69 (CI 0.65-0.72) at T2, and 0.68 (CI 0.63-0.72) at T3. Among pts with available serum biomarkers, no significant associations were observed between inflammatory proteins and CRCI at any time point. Performance of models incorporating inflammatory biomarkers was similar to clinical-only models (Table 2). Conclusions: Almost 1/3 of BC survivors in this cohort reported severe CRCI. This rate was stable throughout the survivorship period and did not seem to be affected by cancer-specific or tx-related factors, or inflammatory biomarkers. Pts age and concomitant symptom burden at dx emerged as consistent associations with severe CRCI. A description of the average population risk of CRCI using a self-reported, global evaluation scale may not fully describe the granularity of this phenomenon. Further studies building on dedicated, objective measurements, may help identify latent classes of pts experiencing a major decline in cognitive function following BC tx, and for whom a contribution of biology may help explain inter-individual variability and underlying biological processes.
Table 1.Models of severe CRCI in the overall cohort: clinical predictors.T1 (N=7724)T2 (N=6825)T3 (N=4706)OR* (95% CI)OR* (95% CI)OR* (95% CI)Severe Pain**, vs no1.50 (1.09-2.07)1.93 (1.39-2.69)1.55 (1.03-2.34)Severe pre-tx CRCI**, vs no3.69 (2.70-5.05)2.53 (1.85-3.46)2.21 (1.47-3.32)Severe Fatigue**, vs no1.50 (1.06-2.11)1.61 (1.13-2.28)1.08 (0.69-1.70)Age (continous)0.98 (0.97-0.99)NR0.98 (0.96-0.99)Menopause, post- vs pre-NR0.73 (0.54-0.98)NRAnxiety, case vs normalNRNR1.82 (1.13-2.92)Anxiety, borderline vs normalNRNR1.84 (1.17-2.91)Hot flashes, vs no1.25 (0.92-1.69)1.20 (0.87-1.65)1.64 (1.10-2.43)Corrected AUC0.73 (0.70-0.76)0.69 (0.65-0.72)0.68 (0.63-0.72)OR= Odds Ratio, CI= Confidence Interval, NR= Not Retained; *Adjusted by BMI, alcohol, smoke, socioeconomic, psychological, tumor and tx; **QLQ-C30
Table 2.Models of severe CRCI in the overall cohort**: biological biomarkers.T1 (N=1094)T2 (N=1091)T3 (N=870)OR* (95% CI)OR* (95% CI)OR* (95% CI)IL6NR0.80 (0.46-1.40)1.01 (0.64-1.60)IL1RA0.66 (0.37-1.17)0.88 (0.50-1.55)NRCRP0.94 (0.60-1.48)1.44 (0.92-2.27)NRIL20.93 (0.55-1.57)1.10 (0.61-1.97)NRIL1βNR1.55 (0.71-3.40)NRIFNγ1.86 (0.69-5.01)0.75 (0.25-2.22)NRIL101.05 (0.34-3.27)1.27 (0.58-2.78)NRIL1A0.71 (0.15-3.33)0.80 (0.17-3.66)NRIL80.96 (0.58-1.58)NRNRTNFαNR1.35 (0.67-2.73)NRMCP-11.07 (0.64-1.78)0.83 (0.51-1.35)0.80 (0.48-1.31)Corrected AUC0.72 (0.67-0.77)0.70 (0.65-0.75)0.67 (0.62-0.72)OR= Odds Ratio, CI= Confidence Interval, NR= Not Retained; *Adjusted by BMI, alcohol, smoke, socioeconomic, psychological, tumor and tx; ** Clinical predictors from previous models were forced in the models at each time-point
Citation Format: Daniele Presti, Florence Joly, Davide Soldato, Stergios Christodoulidis, Antonin Della Noce, Julie Havas, Florine Dubuisson, Barbara Pistilli, Valerie Camara-Clayette, Fabrice André, Anne-Laure Martin, Alexandra Jacquet, Sandrine Boyault, Ivan Bièche, Charles Coutant, Paul-Henry Cournede, Stefan Michiels, Caroline Pradon, Ines Vaz-Luis, Antonio Di Meglio. Cancer-related cognitive impairment (CRCI) in early breast cancer (BC) survivors abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-09.
Background
Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns ...of coffee and tea consumption and association with patient‐reported outcomes (PROs) and clinical outcomes among survivors of BC.
Methods
The authors included survivors of stage I–III BC enrolled in the CANTO cohort (NCT01993498) that provided post‐treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group‐based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes.
Results
Among 3788 patients, the authors identified four stable patterns of consumption: “Low” (25.8%), “Moderate” (37.6%), “High” (25.3%), and “Very high” (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the “Very high” group (vs. “Low”), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups.
Conclusions
Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes.
More than 30% of survivors of breast cancer report high post‐diagnostic consumption of coffee and tea. In this study, the authors did not find any detrimental association between higher consumption of coffee and tea and patient‐reported or clinical outcomes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Background: Higher levels of pre and post-diagnosis physical exercise lead to reduced risk of death among survivors of BC. However, the effect of exercise on recurrence remains unclear. ...Furthermore, previous studies assumed a linear relationship between exercise and clinical outcomes, used discrete classifications of exercise and did not report results according to BC subtype. The aim of this study was to investigate the dose–response relationship of exercise and clinical outcomes among survivors of BC and by BC subtypes. Methods: We included pts diagnosed with stage I-III BC from the CANTO cohort (NCT01993498). CANTO collects longitudinal data, including self-reported exercise exposure using the Global Physical Activity Questionnaire (GPAQ-16), at diagnosis (dx), 1 (T1), 2 (T2) and 4 (T3) years after dx. Exercise exposure in travel and leisure time was calculated according to GPAQ16 guidelines to derive a total MET-hours per week (MET-h/w) at dx and T1 and absolute change in exercise was computed between these timepoints. Outcome of interest was distant relapse-free interval (DRFI) according to STEEP criteria. Restricted cubic splines from unadjusted Cox models assessed the dose-response relationship between exercise and DRFI in the overall cohort and by BC subtype. Kaplan-Meier estimator, log-rank test and multivariate Cox models assessed the prognostic role of exercise. Results: In the overall cohort with available data on exercise at dx (N=10,359) mean (SD) age and BMI were 56.3 (11.2) years and 25.9 (5.4) kg/m2, 38.7% of pts were premenopausal, 52.9% received chemotherapy and 81.9% hormonal therapy, 57.1% were meeting WHO exercise recommendations at dx. At a median (IQR) follow-up of 5.5 (3.9-6.5) years, 541 DRFI events were observed. In the overall cohort, the spline showed a significant non-linear relationship between exercise at dx and DRFI: exposure greater than ≈5 MET-h/w was associated with an inverse linear risk reduction up to ≈25 MET-h/w. A similar relationship was observed in the HR+/HER2- and HR-/HER2- cohorts. On this basis, exercise was categorized as ‘no exercise’ (0 MET-h/w) and ‘exercise’ (≥ 5 MET-h/w). Pts reporting exercise ≥ 5 MET-h/w had longer DRFI compared to those reporting no exercise in the overall (log-rank p< 0.0001), HR+/HER2- (log-rank p< 0.0113) and HR-/HER2- (log-rank p< 0.0001) cohorts. In multivariate analyses, reporting exercise ≥ 5 MET-h/w was associated with a significant lower risk of DRFI events in the overall (HR 0.75, 95%CI 0.62-0.90) and HR-/HER2- cohorts (HR 0.54, 95%CI 0.37-0.80). Absolute change in exercise exposure from dx to T1 was available in 8,516 pts: 34.2% increased exercise (≥ 5 MET-h/w), 25.9% decreased exercise (≤ -5 MET-h/w) and 39.8% maintained exercise ( > –5 and < +5 MET-h/w). The spline showed a non-significant relationship between change in exercise and risk of DRFI events and change in exercise was not significantly associated with risk of DRFI events in multivariate analyses. Conclusions: In this large, prospective cohort of survivors of BC, higher exercise at diagnosis was associated with reduced risk of DRFI events. The relationship between exercise dose and clinical outcomes appears non-linear and to differ based on subtype. Change in exercise after breast cancer diagnosis does not appear to impact on clinical outcomes. Future studies should aim at validating these findings in independent cohorts. XX XX Citation Format: Davide Soldato, Ines Vaz Luis, Julie Havas, Antonio Di Meglio, Neil Iyengar, Barbara Pistilli, Paul Cottu, Florence Lerebours, Charles Coutant, Aurélie Bertaut, Olivier Trédan, Laurence Vanlemmens, Christelle Jouannaud, Ioana Hrab, Sibille Everhard, Anne-Laure Martin, Fabrice André, Lee Jones. Dose-response association between post-diagnosis exercise and clinical outcomes among survivors of breast cancer (BC) abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-07.
Several studies associating single nucleotide polymorphisms (SNPs) frequencies with tumors outcome have been conducted, nevertheless malignant melanoma literature data are inconclusive.Therefore we ...evaluate the impact of different genotypes for phosphoinositide-3-kinase (PI3K) and vitamin D3 nuclear receptor (VDR) SNPs on melanoma patients' outcome.
Genomic DNA of 88 patients was extracted from blood and tumor samples. SNPs were determined by PCR using TaqMan assays. We selected polymorphisms of the regulatory and catalytic subunit of PI3K (PIK3R1 and PIK3CA genes, respectively), analyzing rs2699887C>T of
and rs3730089G>A of
SNPs. Furthermore we considered the following
SNPs: rs2228570A>G (Fok1), rs731236A>G (Taq1) and rs1544410C>T (Bsm1).Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and with Mantel-Haenszel log-rank test.
The statistical analysis for Fok1 of
showed a significant difference in PFS after the first line therapy (median PFS= 21.2 months in the homozygous recessive genotype group vs. 3.3 months of homozygous dominant and heterozygous ones,
= 0.03). In particular, in homozygous recessive patients for Fok1 SNPs of
a high rate of histological regression and BRAF (B- Rapidly Accelerated Fibrosarcoma gene) mutation were observed. Furthermore, more efficacy of BRAF +/- MEK (MAPK-ERK-Kinase) inhibitors therapies in homozygous recessive patients vs. homozygous dominant and heterozygous ones was shown.
Our study showed a significant correlation between homozygous recessive genotype of Fok1 SNPs of VDR gene and an increased PFS in patients who underwent a first line therapy with BRAF inhibitors.
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