Cancer Research Group Research Articles

Rectal Cancer Watch & Wait Management: Experience of 545 Patients from the U.S. Rectal Cancer Research Group.

The use of a watch and wait management strategy following a complete clinical response to neoadjuvant therapy for rectal cancer is increasing. However, insights into implementation, treatments, and outcomes, on a United States national level, are limited. To investigate and report on watch & wait management practices and outcomes in the US. Retrospective study. Multicenter. Stage II or III rectal cancer patients who underwent intentional watch & wait management between January 2015 and August 2022. Patient and tumor characteristics, neoadjuvant treatment and response, local cancer regrowth and metastasis, salvage surgery, overall and disease-specific survival. Among 545 patients from 33 centers, follow-up was 21 months (range, 9-37). Total neoadjuvant therapy or other types of neoadjuvant were used in 395 (72%) and 150 (28%) of patients, respectively. Estimated 3-year local regrowth rate was 23.8% (95% CI: 19.1-29.4%). Patients with local regrowth had higher distant metastases incidence (14.2% vs. 3.5%, p < 0.001). Salvage surgery was performed in 74/84 (88%) patients with local regrowth and included rectal resection in 66 (89%), and local excision in 8 (11%). Of 64 salvage resections with known pathology results, 58 (91%) were margin-negative. Overall, 3-year overall survival was 94.8% (95% CI: 90.5 - 97.2%) and 3-year disease specific survival 96.2% (95% Cl 91.8 - 98.2%). Patients with and without local regrowth exhibited 3-year overall survival of 83.6% (95% Cl 68.4 - 91.9%), and 97.7% (95% CI: 93.3 - 99.2%), respectively. Retrospective study. This multicenter study indicates that the watch & wait approach for locally advanced rectal cancer is feasible with acceptable outcomes across a variety of geographical regions and practice settings in the US. Local regrowth and distant metastasis rates were within published norms and salvage surgery proved effective. See Video Abstract.

Predictive ability of the Cancer and Aging Research Group chemotherapy toxicity calculator in hematologic malignancy

IntroductionChemotherapy toxicity tools are rarely studied in patients with hematologic malignancy (HM). The primary aim of this pilot study was to determine the predictive ability of the Cancer and Aging Research Group (CARG) chemo-toxicity calculator in estimating grade 3–5 toxicity in patients with HM. Materials and MethodsPatients 60 years and older with HM were prospectively evaluated using the CARG chemo-toxicity calculator. Discrimination and calibration were checked by applying the published model in our data. Additionally, a full geriatric assessment (GA), the Short Physical Performance Battery (SPPB), and health related quality of life (HRQoL) were captured longitudinally at the start of treatment and at end of study. Secondary aims explored the association of GA metrics with chemo-related toxicities and survival. ResultsOne hundred forty-five patients were approached, 118 patients consented, and 97 patients were evaluable. Most patients were newly diagnosed (n = 91). The median CARG score was 9 (range 4–18). The CARG score was not validated in our cohort of older patients with HM, with area under the receiver operation characteristic curve being 0.53 (95 % CI: 0.41–0.65). In multivariable analysis, after controlling for disease type, risk factors associated with grade 3–5 toxicity included living alone (hazard ratio [HR] 4.24, 95 %CI: 2.07–8.68, p < 0.001), increase in body mass index (HR 1.06, 95 %CI: 1.01–1.12, p = 0.03) and a higher social activities score (HR 1.27, 95 %CI: 1.06–1.51, p = 0.01). In multivariable analysis of overall survival, the only prognostic factor was an objective marker of physical function (SPPB score HR = 0.85, 95 %CI:0.78–0.93, p < 0.001). DiscussionThe CARG chemo-toxicity calculator was not predictive of grade 3–5 toxicity in patients with hematologic malignancy. The SPPB was associated with overall survival in multivariable analysis, suggesting future use as an objective biomarker in HM. We also report a comprehensive trajectory of function, QoL, psychosocial well-being, and cognition among older adults with HM. The predictive accuracy of the CARG chemo-toxicity calculator may be affected by the diverse range of HM treatment options that are not traditional chemotherapy.

Genomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors.

Our understanding of neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) remains limited. To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Lower PIK3CA, PTEN, and HRAS mutations were found in homologous recombination deficiency (HRD)-high (HRD score ≥ 42) tumors with higher pCR rates. When HRD-high tumors were stratified by tumor BRCA mutation status, the pCR rates in BRCA2-mutated tumors were higher (83% vs. 36%). Transcriptomic profiling of TP53-positive tumors identified downregulation of FGFR2 (false discovery rate p value = 2.07e-7), which was also the only common gene between HRD-high and -low tumors with pCR/quasi-pCR treated with paclitaxel and eribulin combined with carboplatin, respectively. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.

Association of ATM and ARID1A in gastric carcinoma

BackgroundThe ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear. MethodsWe used the mRNA expression data from the Asian Cancer Research Group to construct tissue microarrays (N = 249). Next-generation sequencing (NGS) databases of Samsung Medical Center (SMC) (N = 813) were used to compare genetic alterations. Tissue microarrays were used for ATM and ARID1A immunohistochemistry, and expressions were categorized as “low” and “high.” NGS data from TCGA-STAD (N = 431) were used as independent cohorts for genetic alterations validation. ResultsIn GCs, 32.1% (80/249) of the cases showed low ATM protein expression (ATMlow) and 20.9% (52/249) showed low ARID1A expression (ARID1Alow). ATMlow was significantly associated with older age (P <.01), gross type of tumor (P =.02), histology (P <. 01), lower incidence of perineural invasion (P =.04), lower disease stage (P <.01), microsatellite instability-high (P <.01), and ARID1Alow (P <.01). Furthermore, GCs in the SMC NGS database showed that ATM mutations were significantly correlated with ARID1A mutations (P <.01), and this finding remained significant in TCGA-STAD validation cohort (P <.01). ConclusionATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.

The Tumour Immune Microenvironment Drives Survival Outcomes and Therapeutic Response in an Integrated Molecular Analysis of Gastric Adenocarcinoma.

We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG) and the Tumour Microenvironment Score (TME) to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations. Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG and TME subtypes and applied to 2,202 gastric cancer patients from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model. A propensity score matched analysis was performed to evaluate the subgroup effect of adjuvant chemotherapy on molecular subtypes. A public external cohort comprised of metastatic gastric cancer treated with immunotherapy was used to externally validate the molecular subtypes. Classification models for TCGA, ACRG and TME achieved an accuracy ± standard deviation of 89.5% ± 0.04, 84.7% ± 0.04 and 89.3% ± 0.02, respectively. We identified the TME score as the only significantly prognostic classification system (HR 0.54 [95% CI 0.39, 0.74], global Wald test p<0.001). In our subgroup analysis, patients who received adjuvant chemotherapy achieved greater survival with increasing TME score (HR 0.47 [95% CI 0.29, 0.74], interaction p<0.05). The combination of TME High and microsatellite instability (MSI) scores significantly outperformed MSI as a univariable predictor of immunotherapy response. We conclude that the Tumour Microenvironment Score is a predominate driver of prognosis as well as chemotherapy and immunotherapy-related outcomes in gastric cancer. This paper provides a foundation for additional analyses and translational work.

850MO Phase II randomized trial of chemotherapy followed by surgery and PORT versus surgery and PORT for organ preservation of T3 and T4a (selected T4b) sinonasal squamous cell carcinoma (SNC): A trial of the ECOG-ACRIN cancer research group (EA3163)

850MO Phase II randomized trial of chemotherapy followed by surgery and PORT versus surgery and PORT for organ preservation of T3 and T4a (selected T4b) sinonasal squamous cell carcinoma (SNC): A trial of the ECOG-ACRIN cancer research group (EA3163)

UK national observational cohort study investigating Tolerance of Anti-cancer Systemic Therapy in the Elderly: the TOASTIE study

ObjectiveThe Cancer and Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation study results have varied. The Tolerance of Anti-cancer Systemic Therapy...

Validation of a chemotherapy toxicity prediction model in older adults with cancer in Taiwan.

223 Background: The Cancer and Aging Research Group (CARG) model is established for predicting chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese or non-solid tumor populations. Due to biopsychosocial distinctions in the Taiwanese demographic and inherent disparities between lymphoma and solid tumors, a modified CARG (mCARG) was assessed for its toxicity prediction capabilities. Methods: In this study, 337 consecutive patients aged ≥65 years with solid tumors (N=258) or lymphoma (N=79), slated for first-line chemotherapy, were recruited from a single medical center in Taiwan between 2018 and 2021, with follow-up until December 31, 2021. Patients were categorized into low-, medium-, and high-risk groups based on mCARG, excluding the cancer-type parameter from the original CARG variables. Validation of mCARG involved receiver operating characteristic (ROC) curves, and individual mCARG variables were analyzed using univariate analysis for their impact on chemotherapy toxicities and overall survival. Results: This study included 337 patients (mean age, 70 years; 160 female [47%]; 177 male [53%]) classified as low-(N=112, 33.2%), medium-(N=106, 31.5%), and high-(N=119, 35.3%) risk. Toxicities of grades ≥3 were 41.1%, 50.0%, and 71.4% ( P&lt;0.001), respectively. ROC was 0.665 (95% CI: 0.608–0.722), indicating satisfactory discrimination. However, the lymphoma subgroup exhibited no significant differences in toxicity risk levels (70.0%, 74.1%, and 81.0%; P=0.39). Among mCARG variables, age ≥72 years ( P=0.008), polychemotherapy ( P=0.009), decreased hemoglobin ( P&lt;0.001), falls ( P=0.008), and inability to walk one block ( P=0.01) were associated with toxicities. One-year overall survival rates were 80.6%, 69.4%, and 57.2%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival ( P=0.001). Conclusions: This prognostic study validated the mCARG model in a heterogeneous cancer cohort in Taiwan but failed to do so in the lymphoma subgroup. Although unable to predict all toxicities, mCARG could offer insights into patient survival among older individuals with cancer.

Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear. Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes. Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2-, DUX4-, and KMT2A-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases. Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.

The relationship of mental health symptoms to chemotherapy toxicity risk in older adults with cancer: Results from the geriatric assessment-driven intervention study.

Depression and anxiety are prevalent in older adults with cancer but are often undertreated. Older adults are also at increased risk of chemotherapy toxicity (CT). This study evaluated the impact of depression and anxiety symptoms on severe CT risk in older adults with cancer. This is a secondary analysis of a randomized trial (2:1) evaluating geriatric assessment-driven intervention (GAIN) versus standard of care (SOC) to reduce grade 3+ CT in older adults with cancer. Mental health was assessed via the Mental Health Inventory 13. CT was graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. A total of 605 patients enrolled (402 GAIN; 203 SOC). Overall, 35% were depressed and 47% were anxious. Patients with depression had increased CT in the SOC arm (70.7% vs. 54.3%; p=.02) but not in the GAIN arm (54.3% vs. 48.5%; p=.27). CT was more likely in SOC patients with depression (odds ratio [OR], 2.03; 95% CI, 1.10-3.72). This association persisted after adjusting for Cancer and Aging Research Group toxicity score (OR,1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR,2.00; 95% CI, 1.03-3.85). Depression and CT were not associated in the GAIN arm (OR, 1.26; 95% CI, 0.84-1.91). Anxiety and CT were not associated in either arm. Elevated depression symptoms are associated with increased risk of severe CT in older adults with cancer, which was mitigated with GAIN. This suggests that treating depression symptoms may lower toxicity risk. Future studies are needed to confirm and investigate the impact of depression-specific interventions on outcomes.

A randomized phase III double-blind placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1105)

BackgroundIn 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC.Findings96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43–1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61–1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab.ConclusionsIn this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.Clinical Trial Information: NCT00520975

Evaluating the cancer aging and research group model in predicting immunochemotherapy toxicity among elderly patients with diffuse large B-cell lymphoma

BackgroundThe management of diffuse large B-cell lymphoma (DLBCL) in elderly patients is complicated by an increased risk of treatment-related toxicity associated with aging. This study aimed to validate the effectiveness of the Cancer Aging and Research Group (CARG) model in elderly patients with DLBCL receiving rituximab-based chemotherapy. MethodsIn this prospective study, elderly DLBCL patients (aged 65 years or older) receiving rituximab-based chemotherapy were consecutively assessed between August 2016 and December 2021 at one medical center in Taiwan using the CARG model to predict treatment-related toxicity. Patients were categorized into low-, medium-, and high-risk groups based on their CARG scores. Comparisons were made regarding toxicities and survival rates among these groups. ResultsNinety-one patients, with a median age of 70 years (range 65–96), were included. A substantial 81 % (74 patients) experienced grade 3–5 toxicity. The overall 2-year survival rate was 63.8 % after a median follow-up of 28 months (range, 2–46). The risk of grade 3–5 toxicity was 83 %, 78 %, and 87 %, respectively, among the low-, medium-, and high-risk groups (p = 0.60). The receiver operating characteristic (ROC) curve for CARG was 0.521 (95 % CI, 0.376–0.666), which was significantly lower than that for the Eastern Cancer Oncology Group score (ROC = 0.701, 95 % CI, 0.571–0.831). Similarly, compared with those of low-risk patients, hazard ratios for overall survival were 9.22 (95 % CI, 1.23–69.1; p = 0.031) and 14.6 (95 % CI, 1.90–112; p = 0.010) for medium- and high-risk patients, respectively. ConclusionWhile CARG exhibited limitations in predicting treatment-related toxicity in elderly DLBCL patients, it demonstrated potential efficacy in predicting survival outcomes.

Molecular classifications of gastric cancer and their clinical potential

Gastric cancer if the 5th most common oncological disease in the world and one of the leading causes of death associated with this pathology. In clinical practice, the Lauren classification is widely used for gastric cancer characterization, but it does not provide accurate information on tumor progression and does not allow to select the optimal therapeutic approach. More modern tumor typologies, for example proposed by the The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), are based on profiling of molecular changes in the tumor genome. Currently, several new classifications exist dividing gastric cancer into groups depending on response to different treatment, for example, checkpoint inhibitors or therapy based on activity of pathological pathways associated with immunity, DNA repair, oncogenic and stromal signatures. The proposed typologies improve diagnosis and treatment of this pathology. The review describes currently available classifications of gastric tumors and considers their practical potential.

Assessing the ability of the Cancer and Aging Research Group tool to predict chemotherapy toxicity in older Japanese patients: A prospective observational study

IntroductionThe Cancer and Aging Research Group (CARG) prediction tool was designed in the United States to predict grade ≥ 3 chemotherapy-related adverse events (CRAE) in older patients. However, its usefulness among Japanese people, who have different sensitivities to anticancer drugs and life expectancy, remains unknown. We aimed to prospectively evaluate the utility of the CARG tool for predicting severe CRAE in older Japanese patients with cancer. Material and MethodsPatients with solid tumors aged 65 years and older who commenced anticancer drug regimens from April 2018 to October 2020 were divided into three groups (low, medium, and high-risk) based on their CARG risk scores. Toxicity was prospectively observed by a pharmacist. The primary objective was to evaluate the correlation between the incidence of grade ≥ 3 CRAE and the CARG risk score. The secondary objective was to evaluate hematological and non-hematological toxicities. CRAE incidence was compared among the three groups using a closed testing procedure: (1) Cochran–Armitage test for trend and (2) chi-square test for paired comparison. ResultsThe patients (N = 165) had a median age of 71 years (range: 65–89 years). CRAE in patients divided into low-, medium-, and high-risk groups, based on CARG risk scores, were 39%, 55%, and 82%, respectively (low vs high; p < 0.001, medium vs high; p < 0.01). The incidence of severe hematologic toxicity was 37%, 35%, and 50% in the low-, medium-, and high-risk groups, respectively; the incidence of severe non-hematologic toxicity was 15%, 36%, and 65%, respectively (low vs medium; p < 0.01, low vs high; p < 0.001, and medium vs high; p < 0.01). DiscussionTo our knowledge, this is the first prospective observational study to validate the CARG prediction tool in older Japanese patients with cancer. The CARG risk score may be effective in predicting the development of non-hematologic toxicities. These results should be considered when administering chemotherapy to older Japanese patients with advanced solid tumors.

The FITNESS study: longitudinal geriatric assessment, treatment toxicity, and biospecimen collection to assess functional disability among older adults with lung cancer.

Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity among older adults with lung cancer using a longitudinal comprehensive geriatric assessment (CGA) and molecular biomarkers of aging. This prospective study included adults ≥60years with any newly diagnosed non-small-cell lung cancer. Participants were recruited from central Ohio (2018-2020). Study assessments included the Cancer and Aging Research Group CGA (CARG-CGA), short physical performance battery (SPPB), and the blessed orientation-memory concentration (BOMC) test at baseline, 3, 6, and 12months. Activities of daily living (ADLs) and instrumental ADLs (IADLs), quality of life (QoL, PROMIS 10), and treatment toxicity were captured monthly. Stool and blood were collected to characterize the gut microbiome and age-related blood biomarkers. This study enrolled 50 participants with an average age of 71.7years. Ninety-two percent of participants were Caucasian, 58% were male, and all were non-Hispanic. Most had advanced stage (stage III/IV: 90%; stage I/II: 10%), with adenocarcinoma the predominant histologic subtype (68% vs. 24% squamous). First-line treatments included chemotherapy (44%), immune checkpoint inhibitors (ICIs, 22%), chemotherapy and ICIs (30%), or tyrosine kinase inhibitors (4%). The median baseline CARG toxicity score was 8 (range 2-12). Among patients with treatment-related toxicity (n = 49), 39 (79.6%) cases were mild (grade 1-2), and 10 (20.4%) were moderate to severe (≥ grade 3). Treatment toxicity was greater among those with a CARG score ≥8 (28.0% vs. 13.6%). Higher IADL independence, QoL, and SPPB scores at baseline were positively associated with Candidatus Gastranaerophilales bacterium, Lactobacillus rogosae, and Enterobacteria phage P4. Romboutsia ilealis, Streptococcus, and Lachnoclostridium sp An138 and T cell lag3 and cd8a were associated with worse IADLs, QoL, and SPPB scores at baseline. A longitudinal CGA and biomarker collection is feasible among older adults undergoing lung cancer treatment. Gut microbe and T cell gene expression changes correlated with subjective and objective functional status assessments. Future research will test causality in these associations to improve outcomes through novel supportive care interventions to prevent functional disability.

Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with rituximab ± lenalidomide for MCL

AbstractAlthough initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine plus rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance after induction is often used. Thus, the open-label, randomized phase 2 ECOG-ACRIN Cancer Research Group E1411 trial was designed to test 2 questions: (1) does addition of bortezomib to BR induction (BVR) and/or (2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012 to 2016, 373 previously untreated patients, 87% aged ≥60 years, were enrolled in this trial. At a median follow-up of 7.5 years, there is no difference in the median PFS of BR compared with BVR (5.5 vs 6.4 years; hazard ratio [HR], 0.90; 90% confidence interval [CI], 0.70-1.16). There were no unexpected additional toxicities with BVR treatment compared with BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide did not significantly improve PFS, with median PFS in R vs LR (5.9 vs 7.2 years; HR, 0.84; 90% CI, 0.62-1.15). Most patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with R alone after BR. Nonetheless, the >5-year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by R maintenance as highly effective initial therapy for older patients with MCL. This trial was registered at www.clinicaltrials.gov as #NCT01415752.

Geriatric Oncology: A 5-Year Strategic Plan.

The increasing rate of the older adult population across the world over the next 20 years along with significant developments in the treatment of oncology will require a more granular understanding of the older adult population with cancer. The ASCO Geriatric Oncology Community of Practice (COP) herein provides an outline for the field along three fundamental pillars: education, research, and implementation, inspired by ASCO's 5-Year Strategic Plan. Fundamental to improving the understanding of geriatric oncology is research that intentionally includes older adults with clinically meaningful data supported by grants across all career stages. The increased knowledge base that is developed should be conveyed among health care providers through core competencies for trainees and continuing education for practicing oncologists. ASCO's infrastructure can serve as a resource for fellowship programs interested in acquiring geriatric oncology content and provide recommendations on developing training pathways for fellows interested in pursuing formalized training in geriatrics. Incorporating geriatric oncology into everyday practice is challenging as each clinical setting has unique operational workflows with barriers that limit implementation of valuable geriatric tools such as Geriatric Assessment. Partnerships among experts in quality improvement from the ASCO Geriatric Oncology COP, the Cancer and Aging Research Group, and ASCO's Quality Training Program can provide one such venue for implementation of geriatric oncology through a structured support mechanism. The field of geriatric oncology must continue to find innovative strategies using existing resources and partnerships to address the pressing needs of the older adult population with cancer to improve patient outcomes.

Usability and feasibility of the open-source GeRI platform for remote assessments in older adults with prostate cancer.

e13664 Background: The Geriatric Remote Initiative (GeRI) is an open-source tool to collect patient-generated health data for older adults with cancer. It comprises a WiFi-enabled Raspberry Pi tablet, a Bangle.js 2 wrist accelerometer, and Mi Body Composition Scale 2 for data collection. Following the initial phase where feedback from older cancer survivors and caregivers refined a demonstration GeRI platform, this study deployed a live version of GeRI in advanced prostate cancer patients to evaluate its feasibility and usability. Methods: In this single-arm pilot feasibility and usability study, we evaluated GeRI among ten advanced prostate cancer patients aged ≥65 years undergoing androgen deprivation (ADT) across varied frailty risk categories. Participants interacted with GeRI for ≥12 weeks. Data collection comprised demographics, clinical information, and vulnerability assessment (Cancer and Aging Research Group [CARG] score) from in-clinic surveys. Biometric (wearable/scale) and electronic patient-reported outcomes data from the tablet were securely transmitted to the institution’s HIPAA-compliant cloud. Usability was evaluated using the System Usability Scale (SUS), aiming for an average score of 68 or higher. Feasibility was achieved if ≥6 participants completed at least 50% of all prompted interactions with the system components (surveys, wearable, and weight/bioimpedance) throughout a 12-week study period. Results: Ten men with metastatic hormone-sensitive prostate cancer [median age: 73 years; 40% minority; median of 3 months of ADT exposure (IQR: 2-4.5); 80% had intensified ADT with 60% getting concurrent prostate-directed radiation] engaged with GeRI for a median of 104 days (IQR: 93-131). 40% were vulnerable with a CARG&gt;5. System usability, evaluated by SUS, yielded a mean score of 84 (SD: 12.5). All participants met the feasibility criterion. Deficiencies in obtaining complete 48-hour accelerometry data from 7 participants were noted with only 1 being due to persistent non-wear of the wearable and the remainder due to transmission failure. Conclusions: The GeRI platform exhibited exceptional usability and met all feasibility benchmarks in a geriatric oncology setting, highlighting its potential despite technical hurdles in accelerometry data collection. Further deployment of GeRI is underway [or planned] through an expanded program focusing on other cancer types, including head and neck, and more robust biometric data collection.

Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.

6009 Background: E3311 is a phase II trial of TOS by credentialed surgeons with pathology-driven deintensified post-operative management in HPV+ OPC. Intermediate risk patients were randomized between standard and reduced dose radiation. We present mature outcome data, at median follow up of 52.4 months (m). Methods: Patients were eligible who had resectable cT1-2 stage III/IV AJCC7 p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (Arm A, N=38); those with clear margins, 2-4 + LN, or ENE ≤1mm were randomized to 50Gy (Arm B, N=100) or 60Gy (Arm C, N=108); those with involved margins, &gt;4 + LN, or &gt;1mm ENE received weekly cisplatin 40 mg/m2 and 60-66Gy (Arm D, N=113). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using a log-rank test, stratified by arm for comparisons of primary site and smoking history. Results: Among 359 evaluable patients, 54-m PFS and OS were 90.6% (90% CI: 87.2%, 93.1%) and 95.3% (90% CI: 93.0%, 96.9%). 54-m PFS by arm was: A 93.2% (90% CI: 79.6%, 97.8%); B 94.9% (90% CI: 89.7%, 97.5%); C 90.2% (90% CI: 82.7%, 94.6%) and D 85.5% (90% CI: 77.5%, 90.8%). 54-m OS by arm was: A 97.1% (90% CI: 85.7%, 99.4%); B 97.9% (90% CI: 93.5%, 99.3%), C 95.1% (90% CI: 90.1%, 97.6%) and D 92.5% (90% CI: 86.9%, 95.7%). Among patients in Arm A, 11 had N0 and 27 N1 stage. Median Arm A lymph node yield (LNY) was 29 (11 to 91 LN) and did not differ for patients with/without recurrence (p=0.83). All Arm A recurrences were in N1 patients: 1 at 18 m and 3 at &gt; 40 m. No significant difference in PFS or OS was observed by prescribed radiation dose for intermediate risk patients (Arm B vs. C). Outcome did not differ by primary site of tonsil vs. other OPC (oOPC): 54-m PFS Tonsil 89.3% (90% CI: 84.9%, 92.5%) vs. oOPC 92.9% (90% CI: 87.0%, 96.2%), p=0.28, and 54-m OS Tonsil 94.6% (90% CI: 91.5%, 96.6%) vs oOPC 96.6% (90% CI: 92.4%, 98.5%), p=0.35. Smoking history also did not impact outcome. 54-m PFS was 89.9% (90% CI: 85.9%, 92.9%) for those with ≤10 pack-years (PY) tobacco exposure and 91.7% (90% CI: 83.9%, 95.9%) for those with &gt;10 PY. Conclusions: TOS, neck dissection with deintensified risk-based post-operative management results in outstanding 54-m PFS and OS across all subsites of T1-2 p16+ OPC, irrespective of smoking history. Late recurrence is not increased when post-operative radiation is reduced from 60 to 50Gy for intermediate risk patients. Pathologic &gt;1mm ENE (N=87), involved margin (N=12) or &gt;4 involved LN (N=30) accurately identify patients at increased recurrence risk and outcomes were favorable among such patients. Among patients with favorable pathologic characteristics, a subset with N1 disease are at risk for late recurrence and further characterization of these patients is warranted. Clinical trial information: NCT01898494 .

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study

BackgroundRetrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT.MethodsThis prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels.ResultsFrom Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy.ConclusionsNeither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy.Clinical trial registryClinicalTrials.gov Identifier: NCT01733628.