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  • 1
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    Clinical and mutational profile of ARID1A-mutated gastrointestinal cancers: Duration of response to platinum-based chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e15611-e15611
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e15611-e15611
    Abstract: e15611 Background: ARID1A is mutated in several cancer types, with studies reporting mutations in up to 10% of colorectal cancers (CRC) and as high as 35% of gastric and pancreatic cancers. The ARID1A gene encodes a member of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex and functions as a tumor suppressor. ARID1A has also been implicated in double-stranded DNA repair via both homologous recombination and non-homologous end-joining, potentially conferring platinum sensitivity. We sought to characterize this subset of gastrointestinal (GI) malignancies. Methods: We identified patients with locally advanced or metastatic ARID1A-mutated GI malignancies treated at Massachusetts General Hospital (MGH) by next-generation sequencing. Patients were selected who gave consent to molecular testing and who were enrolled on to a study. We evaluated clinical characteristics and outcomes for patients undergoing treatment at MGH between 2009 and May 2020. The Kaplan-Meier method was used to calculate progression free survival (PFS) to first-line platinum-based chemotherapy. Results: We captured 38 patients with ARID1A-mutated tumors. Median age at diagnosis was 66 (range 31-87) and 63.2% of patients were male (n = 24). Tumor types varied, including CRC (n = 13, 34.2%), esophagogastric (n = 13, 34.2%), pancreatic (n = 6, 15.7%), cholangiocarcinoma (n = 2, 5.3%), small bowel (n = 1, 2.6%), anal (n = 1, 2.6%), and unknown GI primary (n = 2, 5.3%). Most were metastatic at diagnosis (n = 23, 60.5%). The identified ARID1A mutations were each distinct, occurring along the length of the gene and were comprised of missense (n = 10, 26.3%), nonsense (n = 12, 31.6%), frameshift (n = 13, 34.2%), and splice-site (n = 3, 7.9%) mutations. We observed on average 4-5 co-mutations per tumor, with TP53 (n = 25, 65.8%), KRAS (n = 14, 36.8%), APC (n = 11, 28.9%), BRCA2 (n = 7, 18.4%) and BRAF (n = 7, 18.4%) occurring most frequently. Tumors were both microsatellite stable (n = 23, 60%) and microsatellite unstable (n = 7, 18.4%). Most patients (n = 37, 97.4%) received a platinum-based chemotherapy as first-line therapy including FOLFOX (n = 23, 60.5%), FOLFIRINOX (n = 10, 26.3%), gemcitabine/cisplatin (n = 2, 5.3%), carboplatin/5-FU (n = 1, 2.6%), and carboplatin/etoposide (n = 1, 2.6%). Median PFS for first-line platinum based chemotherapy was 14.0 months (CI 8.2-34.7) overall. For patients with CRC, PFS to platinum-based therapy was 14.0 months (CI 4.8-not reached) compared with 9.6 months for non-CRC (CI 7.4-not reached). Conclusions: To our knowledge, this is the first assessment of clinical characteristics and outcomes for ARID1A-mutated GI malignancies. Mutations in ARID1A are highly diverse, without a clear association with tumor type. Future studies assessing response to platinum-based chemotherapy are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e15611
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Noninvasive comprehensive genomic profiling from plasma ctDNA in pancreatic cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. 753-753
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 753-753
    Abstract: 753 Background: The use of comprehensive genomic profiling (CGP) is increasing in pancreatic ductal adenocarcinoma (PDAC) as knowledge improves regarding molecular drivers of tumorigenesis and effective targeted therapies emerge. However, adequate tissue sampling is often limited. Plasma-based CGP offers a non-invasive approach to assess biomarkers that may impact treatment decisions. Methods: We retrospectively evaluated genomic and clinical data from 97 PDAC patients with circulating tumor DNA (ctDNA) testing from 9/2016-8/2019 (Guardant Health, Inc.). ctDNA analysis included single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 74 genes. ctDNA results were assessed across clinical variables. We evaluated for actionable alterations. Results: A total of 114 samples were obtained from 97 patients for ctDNA testing. ctDNA alterations were detected in 82% (93/114) of all samples, including 90% (18/20) at diagnosis, 88% (59/67) at progression, and 56% (10/18) while on stable therapy. ctDNA alterations were found at each stage of PDAC: in 25% (1/4) of samples with resectable disease, 75% (3/4) with borderline resectable disease, 82% (9/11) with locally advanced disease, and 85% (81/95) with metastatic disease. One or more KRAS alterations were detected in 55% (51/93) of patients with alterations present. The median maximum mutant allele frequency was similar between the cohort of patients with KRAS detected (0.55%) versus not detected (0.70%). 8% (8/97) of patients had potentially actionable alterations (2 activating BRAF SNVs, 1 ERBB2 CNV, 1 ERBB2 activating SNV, 1 KRAS G12C, and 3 indels in Homologous Recombination Deficiency genes). Median turnaround time was 8 days. 51% (49/97) of patients had both plasma-based CGP and tissue-based CGP. Of these patients, tissue-based CGP showed ≥ 1 alterations detected in 82% (40/49), test failure in 14% (7/49), and no alterations detected in 4% (2/49). Conclusions: Plasma-based CGP detected ctDNA alterations in 90% of samples tested at diagnosis and 82% of all samples. Potentially actionable mutations were found in 8% of patients, with prompt processing time allowing for rapid decision making.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.753
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Dose intensity of neoadjuvant FOLFIRINOX (FFX) in borderline and locally advanced pancreatic cancer (LAPC): A comparison to the adjuvant benchmark.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 392-392
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 392-392
    Abstract: 392 Background: Optimal timing and duration of FFX for resectable, borderline resectable, and LAPC has not been established. The PRODIGE 24/CCTG PA.6 study used 12 cycles of adjuvant modified FFX (eliminating bolus 5FU, irinotecan at 150mg/m2) demonstrating superior DFS (21.6 mo) over gemcitabine (12.8 mo). However, only 48% of patients (pts) received 70% of intended chemo dosing, and 66.4% of pts completed all doses due to postoperative tolerability. We conducted total neoadjuvant therapy (TNT) studies in borderline and LAPC. (LAPC study included Losartan experimentally.) Dose intensity of TNT with FFX is compared to the benchmark adjuvant data. Methods: In this retrospective analysis, chemotherapy data were analyzed from NCT01821729 (LAPC) and NCT01591733 (Borderline). Both studies included 8 cycles of neoadjuvant FFX: b5FU 400mg/m2, CI 5U 1200mg/m2/d x 2d, oxaliplatin 85mg/m2, and irinotecan 180mg/m2. Results: 92 pts were studied: Borderline n = 43, LAPC n = 49. Sixteen of 92 (17.3%) patients discontinued chemotherapy prior to 8 cycles due to: withdrawal of consent (2), chemotherapy toxicity (6), progression (4), and disease-related complications (4). 82.6% of patients completed 8 doses. 61.4% of all bFU was given at the intended dose of 400 mg/m2. The mean relative dose intensity of b5FU (the actual cumulative dose relative to the planned cumulative dose over 8 cycles) was 72%. 65.5% of patients required a reduction in b5FU over eight cycles. Data for all chemotherapy are presented in Table 1. Overall, 71 of 92 patients (77.2%) had 〉 70% dose of FFX, with mean relative dose intensity of 81.2%. Among surgically resected patients, mPFS was 21.3 months in LAPC (n = 34) and 48.6 months in Borderline (n = 33). Conclusions: Compared to adjuvant therapy, dose intensity was achieved in a higher proportion of participants with TNT, utilizing a FFX regimen that included b5FU and irinotecan at 180mg/m2. PFS among resected patients reflects this highly active treatment. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.392
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Use of patient-reported outcomes (PROs) to predict treatment outcomes in patients with advanced cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 29_suppl ( 2020-10-10), p. 186-186
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 29_suppl ( 2020-10-10), p. 186-186
    Abstract: 186 Background: PROs assessing quality of life (QOL) and physical symptoms often correlate with clinical outcomes in patients (pts) with cancer. Yet, data are lacking about the use of PROs to predict treatment response. We evaluated associations of baseline PROs with treatment response, healthcare use, and survival among pts with advanced gastrointestinal cancer. Methods: We prospectively enrolled pts with metastatic gastrointestinal cancer prior to initiating chemotherapy at Massachusetts General Hospital. At baseline (start of treatment), pts reported their QOL (Functional Assessment of Cancer Therapy General [FACT-G], subscales assess QOL across 4 domains: functional, physical, emotional, social well-being) and symptom burden (Edmonton Symptom Assessment System [ESAS] ). Higher scores on FACT-G indicate better QOL, while higher scores on ESAS represent a greater symptom burden. We used regression models to examine associations of baseline PRO scores with treatment response (clinical benefit [CB] or progressive disease [PD] at the time of first scan based on clinical documentation), healthcare use (unplanned hospital admissions), and survival. Results: From 5/2019-3/2020, we enrolled 112 of 131 (85.5% enrollment) consecutive pts (median age = 62.8, 61.6% male, 45.5% pancreatobiliary cancer). For treatment response, 64.3% had CB and 35.7% had PD. Higher ESAS-physical (B = 1.04, p = .027) and lower FACT-G functional (B = 0.92, p = .038) scores at baseline were significant predictors of PD. On the specific ESAS items, pts who experienced PD were more likely to report moderate/severe poor well-being (57.9% vs 29.7%; p = .001), pain (44.7% vs 25.0%; p 〈 .050), drowsiness (42.1% vs 20.3%; p = .024), and diarrhea (23.7% vs 4.7%; p = .008) at baseline. Lower FACT-G total (HR = 0.96, p = .003), FACT-G physical (HR = 0.89, p 〈 .001), FACT-G functional (HR = 0.87, p 〈 .001), and higher ESAS-physical (HR = 1.03, p = .028) scores at baseline were significantly associated with greater risk of hospital admission. Lower FACT-G total (HR = 0.96, p = .009), FACT-G emotional (HR = 0.87, p = .014), as well as higher ESAS-total (HR = 1.03, p = .018) and ESAS-physical (HR = 1.03, p = .040) scores at baseline were significantly associated with greater risk of death. Conclusions: We found that baseline PROs predict treatment response in pts with advanced cancer, namely physical symptoms and functional QOL, in addition to healthcare use and survival outcomes. These findings further support the use of PROs to predict important clinical outcomes, including the novel finding of treatment response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.29_suppl.186
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Changes in patient-reported outcomes (PROs) and tumor markers (TMs) to predict treatment response and survival in patients with metastatic gastrointestinal (GI) cancer.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 28_suppl ( 2021-10-01), p. 154-154
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 28_suppl ( 2021-10-01), p. 154-154
    Abstract: 154 Background: PROs assessing quality of life (QOL) and symptoms at a single timepoint frequently correlate with clinical outcomes in patients with cancer, yet efforts to understand how longitudinal changes in PROs can predict for treatment outcomes are lacking. In practice, oncologists often use changes in serum TMs (CEA and CA19-9) to monitor patients with GI cancer, and thus we sought to examine associations of 1-month changes in PROs and TMs with treatment response and survival outcomes among patients with advanced GI cancer. Methods: We prospectively enrolled patients with metastatic GI cancer prior to initiating chemotherapy at Massachusetts General Hospital from 5/2019-12/2020. At baseline (start of treatment) and 1-month later, we collected PROs (QOL [Functional Assessment of Cancer Therapy General {FACT-G}], physical symptoms [Edmonton Symptom Assessment System {ESAS}] , and psychological symptoms [Patient Health Questionnaire-4 {PHQ-4}]) and TMs. We used regression models to examine associations of 1-month changes in PROs and TMs with treatment response (clinical benefit [defined as decreased or stable tumor burden] or progressive disease at the time of first scan) and survival outcomes (progression-free survival [PFS] and overall survival [OS] ), adjusted for baseline values of each respective variable. Results: We enrolled 159 of 191 patients approached (83.2% enrollment); 134 had 1-month follow-up data (median age = 64 years [range: 28 to 84 years], 64.2% male, 46.3% pancreaticobiliary cancer). For treatment response, 63.4% had clinical benefit and 36.6% had progressive disease at the time of first scan (mean time to first scan = 2.01 months). Changes in PROs (ESAS-Total: OR = 0.97, p = 0.022; ESAS-Physical: OR = 0.96, p = 0.027; PHQ-4 depression: OR = 0.67, p = 0.014; FACT-G: OR = 1.07, p = 0.001), but not TMs (CEA: OR = 1.00, p = 0.836 and CA19-9: OR = 1.00, p = 0.796), were associated with clinical benefit at the time of first scan. Changes in ESAS-Total (HR = 1.03, p = 0.004), ESAS-Physical (HR = 1.03, p = 0.021), PHQ-4 depression (HR = 1.22, p = 0.042), FACT-G (HR = 0.97, p = 0.003), and CEA (HR = 1.00, p = 0.001) were predictors of PFS. Changes in ESAS-Total (HR = 1.03, p = 0.006) and ESAS-Physical (HR = 1.04, p = 0.015) were predictors of OS, but 1-month changes in TMs (CEA: HR = 1.00, p = 0.377 and CA19-9: HR = 1.00, p = 0.367) did not significantly predict for OS. Conclusions: We found that 1-month changes in PROs can predict for treatment response and survival outcomes in patients with advanced GI cancers. Notably, 1-month changes in CEA only correlated with PFS, while changes in CA19-9 did not significantly predict treatment response or survival outcomes. These findings highlight the potential for early changes in PROs to predict treatment outcomes while underscoring the need to monitor and address PROs in patients with advanced cancer. Clinical trial information: NCT04776837.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.39.28_suppl.154
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Local and systemic recurrence following total neoadjuvant therapy (TNT) and resection for borderline resectable and locally advanced pancreatic adenocarcinoma: Long-term follow up from two phase II studies.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 4133-4133
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 4133-4133
    Abstract: 4133 Background: With the advent of FOLFIRINOX, the management of pancreatic cancer has undergone a profound change. There has been a shift to TNT with FOLFIRINOX followed by radiation and an attempt at surgical resection. Recent trials of TNT have demonstrated an ability to resect locally advanced (LA) and borderline resectable disease. There is a lack of prospective data demonstrating local and systemic recurrence rates after TNT. Methods: Two previously reported prospective clinical trials (Murphy JE, et al, JAMA Oncol 2018, 2019) of total neoadjuvant therapy were conducted between 2012 and 2018 for borderline and LA disease (NCT01591733, NCT01821729). Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy x 5 with protons or 3 Gy x 10 w photons) with capecitabine (N=34). Patients with persistent vascular involvement received long-course chemoradiotherapy with capecitabine (N=56). All patients were considered for resection after TNT except for those patients with metastatic or unresectable disease. Results: 97 eligible patients were enrolled and started treatment on the borderline resectable (n = 48) and locally advanced (n= 49) study. 90 patients completed therapy. 80 patients were taken to the operating room. 61 patients had R0 resection and 5 patients had R1 resection. The table shows the distribution of local recurrences, local recurrences and metastatic disease, and metastatic disease alone. With a median follow-up of 5.2 years (range: 2.4-6.0), of the 61 R0 patients, 22 patients remained alive and free of disease, 7 patients had a local recurrence, 4 patients had locoregional and metastatic recurrence, and 24 patients had a metastatic recurrence. 3 patients who underwent R0 resection died of unrelated causes. Median survival for patients undergoing R0 resection is 43.8 months. Conclusions: Total neoadjuvant therapy for locally advanced and borderline resectable pancreatic cancer is potentially curable and may change the pattern of spread.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.4133
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 7
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    A phase II study of ipilimumab and nivolumab with radiation in metastatic pancreatic adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 391-391
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 391-391
    Abstract: 391 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer. Immunotherapy (IO) has shown minimal activity. In preclinical models, radiation (XRT) increases likelihood of response to IO via an abscopal effect where local tx (treatment) of a tumor leads to an antitumor response distantly, with synergy between XRT and dual checkpoint blockade. In this study, we assessed CTLA-4 and PD-1 blockade with XRT as a strategy to stimulate an immune response for patients (pts) with PDAC. Methods: In this open-label, single arm phase-2 study, we enrolled 25 metastatic PDAC pts in an exploratory cohort. Eligible pts had histologically-confirmed PDAC, ECOG PS 0-1, and progression on at least 1 line of tx. Tx consisted of Ipilimumab (1 mg/kg every 6 wks), Nivolumab (240 mg every 2 wks) and 3 fractions of 8 Gy of XRT at cycle 2. Tx continued until PD, discontinuation or withdrawal. Endpoints include Disease Control Rate (DCR), ORR, PFS, OS and safety. Radiological evaluations were every 3 months. Response was defined as disease control outside of the radiation field. We obtained serial tumor biopsies pre-tx, during checkpoint blockade alone and 2 weeks after XRT. Intention to treat analysis includes all pts receiving at least one dose of study tx. Results: 22 pts were enrolled and evaluable from 6/2017-6/2018, median age 60 years (32-75), 73% male and 100% MSS. DCR was 27% and ORR was 14% with 1 pt having a complete response. All responses were out of the radiation field. Median PFS was 76 days in the entire cohort; 163 days for pts with disease control vs 62.5 days for pts with PD or who came off study prior to initial imaging. 7 pts did not receive XRT due to clinical progression. Treatment-related adverse events (AEs) were reported in 12/22 pts (54.5%). 8/22 pts (36.4%) experienced grade ≥ 3 toxicities. Elevated lipase, lymphopenia, fatigue, hyperglycemia, mucositis and hepatitis were the most common AEs. 1/22 (4.5%) pt had a grade 5 AE possibly related to tx. Conclusions: Dual blockade of CTLA-4 and PD-1 with XRT is feasible and demonstrates promising activity in pts with metastatic PDAC. We will report the updated efficacy and safety data as well as outcomes from the correlative serial biopsies upon completion. Clinical trial information: NCT03104439.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.391
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 8
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    Changes in patient-reported outcomes (PROs) and tumor markers (TMs) to predict treatment response and survival outcomes in patients with metastatic gastrointestinal (GI) cancer.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 6560-6560
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 6560-6560
    Abstract: 6560 Background: PROs assessing quality of life (QOL) and symptoms at a single timepoint frequently correlate with clinical outcomes in patients with cancer, yet efforts to understand how longitudinal changes in PROs can predict for treatment outcomes are lacking. In practice, oncologists often use changes in serum TMs (CEA and CA19-9) to monitor patients with GI cancer, and thus we sought to examine associations of 1-month changes in PROs and TMs with treatment response and survival outcomes among patients with advanced GI cancer. Methods: We prospectively enrolled patients with metastatic GI cancer prior to initiating chemotherapy at Massachusetts General Hospital from 5/2019-12/2020. At baseline (start of treatment) and 1-month later, we collected PROs (QOL [Functional Assessment of Cancer Therapy General {FACT-G}] , physical symptoms [Edmonton Symptom Assessment System {ESAS}], and psychological symptoms [Patient Health Questionnaire-4 {PHQ-4}] ) and TMs. We used regression models to examine associations of 1-month changes in PROs and TMs with treatment response (clinical benefit [defined as decreased or stable tumor burden] or progressive disease at the time of first scan) and survival outcomes (progression-free survival [PFS] and overall survival [OS]), adjusted for baseline values of each respective variable. Results: We enrolled 159 of 191 patients approached (83.2% enrollment); 134 had 1-month follow-up data (median age = 64 years [range: 28 to 84 years] , 64.2% male, 46.3% pancreaticobiliary cancer). For treatment response, 63.4% had clinical benefit and 36.6% had progressive disease at the time of first scan (mean time to first scan = 2.01 months). Changes in PROs (ESAS-Total: OR = 0.97, p = 0.022; ESAS-Physical: OR = 0.96, p = 0.027; PHQ-4 depression: OR = 0.67, p = 0.014; FACT-G: OR = 1.07, p = 0.001), but not TMs (CEA: OR = 1.00, p = 0.836 and CA19-9: OR = 1.00, p = 0.796), were associated with clinical benefit at the time of first scan. Changes in ESAS-Total (HR = 1.03, p = 0.004), ESAS-Physical (HR = 1.03, p = 0.021), PHQ-4 depression (HR = 1.22, p = 0.042), FACT-G (HR = 0.97, p = 0.003), and CEA (HR = 1.00, p = 0.001) were predictors of PFS. Changes in ESAS-Total (HR = 1.03, p = 0.006) and ESAS-Physical (HR = 1.04, p = 0.015) were predictors of OS, but 1-month changes in TMs (CEA: HR = 1.00, p = 0.377 and CA19-9: HR = 1.00, p = 0.367) did not significantly predict for OS. Conclusions: We found that 1-month changes in PROs can predict for treatment response and survival outcomes in patients with advanced GI cancers. Notably, 1-month changes in CEA only correlated with PFS, while changes in CA19-9 did not significantly predict treatment response or survival outcomes. These findings highlight the potential for early changes in PROs to predict treatment outcomes while underscoring the need to monitor and address PROs in patients with advanced cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.6560
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Aggressiveness of care and overall survival in young metastatic colorectal cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3563-3563
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3563-3563
    Abstract: 3563 Background: Colorectal cancer (CRC) incidence in patients younger than 50 years of age is steadily rising by 2% annually. Early-onset CRC usually presents with more aggressive features; however, data on prognosis are widely conflicting. Clinicians may hold an age-related bias in treating younger patients, but this proclivity and its effects have not been quantified. Methods: Patients with a history of metastatic CRC who consented to a departmental chart review protocol were collected between 2014 and 2018 at Massachusetts General Hospital. The cohort was divided into two groups based on age at initial diagnosis: 〈 50 and ≥50. Data were gathered on treatments and clinicopathological features. A log-rank test compared survival from the diagnosis of metastatic disease between age groups. The distributions of clinicopathological features were compared using Wilcoxon rank sum tests. Results: 464 metastatic CRC patients were identified. 155 patients (33%) were 〈 50 (median age 43, 49% female) and 309 patients (67%) were ≥50 (median age 61, 45% female). Sex did not significantly differ between the two groups (p = 0.45). Patients 〈 50 received more lines of therapy after metastatic diagnosis than patients ≥50 (mean 2.7 v. 2.2; p = 0.002). Younger patients also received more resections of distant metastases (mean 0.62 v. 0.48; p = 0.01). A higher rate of enrollment in clinical trials for patients 〈 50 approached significance (p = 0.06). Even so, patients 〈 50 did not see a significant survival benefit over older patients (2/5-year survival from metastatic diagnosis 77%/47% v. 73%/38%, p = 0.23). Patients 〈 50 had a lower proportion of right-sided tumors (p = 0.0002) and BRAF mutations (p = 0.0009). There was no difference in MSI status (p = 0.28), RAS mutational status (p = 0.40), mucinous features (p = 0.53), or signet ring features (p = 0.26). Conclusions: Overall survival in patients 〈 50 is similar to patients ≥50, despite patients 〈 50 receiving more aggressive therapy. Further study is warranted to better understand these differences. Potential areas of interest include performance status, age-related treatment bias, and biological factors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3563
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Symptom burden to predict health care utilization in hospitalized patients with incurable cancer.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 26_suppl ( 2016-10-09), p. 98-98
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 26_suppl ( 2016-10-09), p. 98-98
    Abstract: 98 Background: Patients with incurable cancer are often hospitalized and have frequent readmissions after discharge. Considering the high physical and psychological symptom burden in this population, we sought to investigate symptoms as predictors of hospital length of stay (LOS) and time to first unplanned readmission. Methods: We consecutively enrolled incurable cancer patients with unplanned hospital admissions from 9/2014-4/2016. Within the first 5 days of admission, we assessed physical (Edmonton Symptom Assessment System [ESAS]; scored 0-10) and mood symptoms (Patient Health Questionnaire 4 [PHQ-4] ; scored categorically). We created summated ESAS total and physical symptom variables. To identify predictors of LOS we used linear regression and for time to readmission we used Cox regression, with all models adjusted for age, sex, marital status, comorbidity, education, cancer type and time since incurable diagnosis. Results: We enrolled 1,000 of 1,227 (81%) eligible patients (mean age = 63.4; 50% female; 66% married). Gastrointestinal (33%) and lung (18%) cancers were the most common. Mean hospital LOS was 6.2 days and 30-day readmission rate was 25%. Over half of patients reported moderate/severe fatigue, drowsiness, lack of appetite, pain and poor well-being. Over one-fourth screened positive for PHQ depression and anxiety. All physical and mood symptoms individually predicted for longer LOS. Pain, nausea, poor well-being, ESAS total, ESAS physical and PHQ anxiety predicted for shorter time to readmission. Conclusions: Hospitalized patients with incurable cancer experience a high symptom burden, which correlates with their health care utilization. Both physical and psychological symptoms predict for longer hospital LOS and shorter time to readmission. These findings can inform interventions targeting patients’ symptoms during hospital admissions in an effort to improve health care delivery and utilization. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.26_suppl.98
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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