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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e15601-e15601
    Abstract: e15601 Background: We evaluated demographic, treatment, and survival outcomes of adults age 18 to 49 years treated at our institution with long course chemoradiotherapy (CRT) followed by total mesorectal excision (TME) for locally advanced rectal cancer. Additionally, we compared outcomes between those age 〈 45 vs. 〉 45 years. Methods: The records of 219 patients diagnosed with non-metastatic, clinical T3, T4, or node positive rectal adenocarcinoma and treated between April 2000 and November 2017 were reviewed for age, sex, and presenting symptoms; clinical stage and microsatellite stable (MSS)/DNA mismatch repair (MMR) proficiency status; treatments delivered and sequence; pathologic response to pre-operative therapies; and the development of locoregional recurrence (LRR), distant metastasis (DM), and secondary pelvic malignancy. The Kaplan-Meier method and Log-Rank test were used to calculate and compare disease-free survival (DFS) and overall survival (OS) rates from the date of TME. Results: The median age at diagnosis was 44 years (range 19-49) and there was no sex predominance. Rectal bleeding was the most common presenting symptom (91%), with a median time to diagnosis of 5 months. Clinical tumor/nodal categories were T1-2 in 4%, T3 in 87%, T4 in 7%, N0 in 17%, and N1–2 in 80% of patients. MSS/MMR proficient disease was identified in 95% of tumors with status reported (n = 170). CRT followed by TME and post-operative chemotherapy was the most frequent treatment sequence (n = 196), with capecitabine (n = 176) and FOLFOX (n = 115) as the predominant concurrent and post-operative chemotherapies, respectively. Pathologic complete response at both primary and nodal sites occurred in 15% of all cases and 16% of MSS/MMR proficient cases. There was no difference in sex, tumor category, nodal category, MSS/MMR proficiency status, or pathologic complete response, by age ( 〈 45 years [n = 111] vs. 〉 45 years [n = 108]). At a median DFS follow-up time of 5.0 years, there were 11 LRR, 40 DM (including 11 DM detected prior to/at time of TME), and 1 synchronous presentation of LRR and DM. The 5-year rate of DFS was 70.4% for age 〈 45 years and 85.3% for age 〉 45 years ( P = 0.02). At an OS median follow-up time of 7.5 years, there were 38 deaths. The 5-year rate of OS was 87.7% for age 〈 45 years and 94.4% for age 〉 45 years ( P = 0.126). Two patients developed non-rectal pelvic malignancies. Conclusions: The outcomes reported here from one of the largest single-institution series for young-onset, locally advanced rectal cancer could serve as a benchmark to evaluate newer treatment approaches. Rectal bleeding was the leading presenting symptom, with approximately half-year delay from development of symptoms to diagnosis. Most tumors were MSS/MMR proficient. At 5 years’ follow-up time, the DFS rate was lower for patients age 〈 45 years when compared to those 〉 45 years. Secondary pelvic malignancies were a rare occurrence.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 3556-3556
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 3556-3556
    Abstract: 3556 Background: Evidence regarding adjuvant chemotherapy (CTx) for patients with rectal cancer after preoperative chemoradiotherapy (CXRT) is limited. The aim of study was to explore the relationship between CXRT response and adjuvant CTx for patients with rectal cancer treated by CXRT and radical resection. Methods: We performed a retrospective consecutive cohort study of patients with locally advanced (cStage II-III by EUS, CT, or MRI) rectal carcinoma treated with preoperative CXRT and radical resection, 1993 to 2008. To explore the late effects, we performed a landmark analysis of patients alive without recurrence at 24 months. The duration free from recurrence (FFR) was compared among patients with complete (CR, ypT0N0), intermediate (IR, ypT1-2N0), or poor (PR, ypT3-4 or N+) response according to adjuvant CTx use and type using multivariate Cox regression. Results: A total of 725 patients met criteria and were evaluated. Median follow-up was 69 months (IQR: 39-104 months). 611 patients received adjuvant CTx: 447 with fluoropyrimidine only (FP), and 139 also received oxaliplatin (Ox). Although receipt of adjuvant chemotherapy was not associated with 5-year FFR overall, (HR: 0.91, 95% CI: 0.58-1.43), adjuvant therapy did appear to suggest a benefit in the IR group (HR, 0.49; 95%CI, 0.21-1.19). 2-year landmark analysis showed that adjuvant CTx was associated with a significant improvement in FFR among the IR patients only (HR, 0.28; 95% CI, 0.08-1.00, p=0.04). Among PR patients FP alone did not improve FFR (HR, 1.22; 95% CI, 0.7-2.12) but the addition of Ox was associated with a non-significant reversal in the direction of the effect (HR, 0.53; 95% CI, 0.16-1.79). Conclusions: In this exploratory analysis, the addition of adjuvant FP CTx appeared to favorably affect the duration FFR only for patients with rectal cancer and intermediate response to CXRT followed by radical resection. These data support the investigation of the role for adjuvant fluoropyrimidine therapy among patients with CR or IR and the addition of oxaliplatin for PR patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Clinical Colorectal Cancer, Elsevier BV, Vol. 21, No. 1 ( 2022-03), p. e28-e37
    Type of Medium: Online Resource
    ISSN: 1533-0028
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2572502-6
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 557-557
    Abstract: 557 Background: Evidence regarding adjuvant chemotherapy (CTx) for patients with rectal cancer after preoperative chemoradiotherapy (CXRT) is limited. The aim of study was to explore the relationship between CXRT response and adjuvant CTx for patients with rectal cancer treated by CXRT and radical resection. Methods: We performed a retrospective consecutive cohort study of patients with locally advanced (cStage II-III by EUS, CT, or MRI) rectal carcinoma treated with preoperative CXRT and radical resection, 1993 to 2008. To explore the late effects, we performed a landmark analysis of patients alive without recurrence at 24 months. The duration free from recurrence (FFR) was compared among patients with complete (CR, ypT0N0), intermediate (IR, ypT1-2N0), or poor (PR, ypT3-4 or N+) response according to adjuvant CTx use and type using multivariate Cox regression. Results: A total of 725 patients met criteria and were evaluated. Median follow-up was 69 months (IQR: 39-104 months). 611 patients received adjuvant CTx: 447 with fluoropyrimidine only (FP), and 139 also received oxaliplatin (Ox). Although receipt of adjuvant chemotherapy was not associated with 5-year FFR overall, (HR: 0.91, 95% CI: 0.58-1.43), adjuvant therapy did appear to suggest a benefit in the IR group (HR, 0.49; 95%CI, 0.21-1.19). Adjusted landmark analysis showed that adjuvant CTx was associated with a significant improvement in FFR among the IR patients only (HR, 0.28; 95% CI, 0.08-1.00, P=.04). Among PR patients FP alone did not improve FFR (HR, 1.22; 95% CI, 0.7-2.12) but the addition of Ox was associated with a non-significant reversal in the direction of the effect (HR, 0.53; 95% CI, 0.16-1.79). Conclusions: In this exploratory analysis, the addition of adjuvant FP CTx appeared to favorably affect the duration FFR only for patients with rectal cancer and intermediate response to CXRT followed by radical resection. These data support the investigation of the role for adjuvant fluoropyrimidine therapy among patients with CR or IR and oxaliplatin for PR patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 645-645
    Abstract: 645 Background: A major goal of surveillance following curative resection for CRC is identification of treatable recurrence. However, there is a paucity of data regarding optimal frequency or duration of surveillance or potential for salvage therapy following detection of recurrence. The aim of this study was to examine treatment patterns following recurrence of CRC. Methods: Patients ≥ 18 years who presented to 8 participating NCCN institutions between 2005-2012 with resected stage I, II, or III CRC were identified. Time to recurrence was determined by the Kaplan-Meier method and descriptive statistics were used to report treatments following recurrence. Results: Of 5653 patients who underwent resection for locoregional CRC (2984 colon, 2669 rectal and rectosigmoid), median age was 60 [IQR: 50-70]. 53.5% were male. With a median follow-up time after diagnosis of 23.5 months (11.0-45.2), 641 recurrences (6.9% local; 93.1% distant) were identified. Median time to local recurrence was 16.1 months [IQR: 12.5-27.3] . Median time to distant recurrence was 15.6 months [IQR: 11.2-23.9]. Among 325 recurrences of a colon primary, 18 (5.5%) were local and 307 (94.5%) were distant; liver and lung were most common sites (30.8% and 13.9%, respectively). Among 316 recurrences of a rectal primary, 26 (8.2%) were local and 290 (91.8%) were distant; lung and liver were most common sites (35.8% and 21.8%, respectively). Of 597 patients who developed a metastatic recurrence, 227 (38.0%) underwent metastectomy (79 liver and 76 lung resections) and 26 (4.3%) underwent ablation. 414 (64.6%) received chemotherapy and 64 (10%) received radiation. 133 (20.7%) died without treatment 〈 1 year after recurrence. Of 641 patients,113 (17.6%) had synchronous sites of recurrence and 152 (23.7%) developed recurrence at a second site within 12 months. Conclusions: A high rate of metastectomy was observed following detection of recurrence within the NCCN hospitals. However, a significant proportion of patients had a second site of recurrence 〈 12 months after initial recurrence. Further inquiry into optimal surveillance and management of recurrence for patients following curative resection of CRC is needed. (Support: U10CA180821, CE-1304-6543).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e15533-e15533
    Abstract: e15533 Background: There is growing evidence for the efficacy of a watch-and-wait or nonoperative management (NOM) strategy following chemoradiation with or without total neoadjuvant therapy for rectal cancer as an approach to organ preservation. Consequently, there has been growing interest and acceptance of this approach among both patients and providers. This study aims to analyze the use of the NOM strategy for patients with non-metastatic rectal cancer over the past decade and the patient and facility-level factors associated with its utilization. Methods: We performed an observational cohort study identifying patients from the National Cancer Database diagnosed between 2010-2020 with invasive, non-metastatic rectal adenocarcinoma. Patients who received chemotherapy and radiation without surgery were categorized as having received NOM. All other patients who received curative-intent surgery with or without chemotherapy and radiation were classified as the standard of care (SOC) cohort. Utilization of NOM was analyzed over time. Logistic regression analysis was utilized to identify patient and facility-level factors associated with NOM. Results: In total, 107,786 patients were included for analysis, of which 14,870 (13.8%) received NOM over the study period and 92,916 (86.2%) received SOC. The use of NOM steadily increased over the study period, from 10.3% in 2010 to 20.7% in 2020. Compared to SOC, NOM was associated with patients who were Black (16.9% vs 13.6% White, p 〈 0.001), had Medicaid or no insurance (15.3% vs 13.4% Private/Medicare insurance, p 〈 0.001), were older than 75 years (18.9% vs 12.8% younger than 75, p 〈 0.001), and had high Charlson-Deyo comorbidity score (16.2% vs 14.0% no comorbidities, p 〈 0.001). Facility factors associated with greater use of NOM included treatment at community cancer programs (OR 1.44, 95% CI 1.35-1.54, p 〈 0.001) compared to treatment at comprehensive cancer centers. Facilities stratified by incident rectal cancer patient volume demonstrated an inverse relationship with NOM management, with low volume institutions having the highest NOM rate (p 〈 0.001). Subgroup analysis of patients 〈 75 years old, with private insurance, and without co-morbidities treated at institutions in the top quartile of volume showed NOM rates to similarly increase over the study period, from 6.4% to 13.7% (p 〈 0.001). Conclusions: The use of the NOM strategy for patients with non-metastatic rectal cancer has increased over the past decade. While traditionally an approach for patients who were poor surgical candidates, the increasing trend for NOM among younger patients with fewer comorbidities and private insurance suggests that there is growing interest in elective NOM over the past decade. Ongoing prospective studies of NOM will shed light regarding the long-term efficacy of this approach compared to traditional surgical SOC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 4_suppl ( 2012-02-01), p. 575-575
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 575-575
    Abstract: 575 Background: Microsatellite instability (MSI) testing in colorectal cancer (CRC) provides prognosis, predicts chemotherapy response, and guides diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MSI can be sporadic or hereditary, arising from somatic or germline mutations in DNA mismatch repair (MMR) genes respectively. The clinical implications of these distinct mechanisms are uncertain. Methods: Patients who underwent MSI testing for CRC between 2000 and 2011 were identified. MSI-high (MSH) CRCs were defined by: pathogenic mutation in MMR genes; 〉 30% of markers with allelic shift in PCR-based MSI testing; or loss of expression in at least 1 MMR protein on immunohistochemistry. The subset with MLH1 gene promoter methylation, BRAF mutation, or EPCAM mutation was considered sporadic. Clinicopathologic features and disease-free survival (DFS) were examined in reference to microsatellite stable (MSS) CRCs. Results: MSH CRC’s, 92 germline and 49 sporadic, were compared with 105 MSS CRCs. Compared to MSS CRCs, both germline and sporadic MSH CRCs more commonly arose in the proximal colon (63% and 92%, vs. 30%; p 〈 .001), exhibited mucinous/signet ring histology (40% and 47%, vs. 16%; p 〈 .001) and lymphocytic infiltrate/Crohn’s like reaction (15% and 49%, vs. 8%; p 〈 .001). Further comparison between germline vs. sporadic MSH CRCs revealed significant differences in median age (44 yrs. vs. 66; p 〈 .001), proximal colon tumor location (63% vs. 91%; p 〈 .001), AJCC stage (33% vs. 51% Stage III or IV; p 〈 .025) and presence of lymphocytic/Crohn’s like reaction (49% vs. 15%, p 〈 .001). Moreover, sporadic MSH CRCs more often had poor prognostic features including poor differentiation (51% vs. 28% in germline, p 〈 .025) and lymphovascular invasion (57% vs. 34% in germline, p 〈 .007). No difference was observed in stage-stratified DFS between germline vs sporadic MSH CRCs. Conclusions: Patients with sporadic MSH CRCs exhibit distinct clinicopathologic features compared to those with germline MSH tumors. Despite poor prognostic features, no apparent survival difference was observed. Further characterization of these distinct groups is warranted to explain the discordance between risk factors and outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 396-396
    Abstract: 396 Background: The optimal strategy to detect HNPCC in CRC pts remains controversial, and may include testing tumors for microsatellite (MSI) status and/or pts for mutations in DNA mismatch repair (MMR) genes. Costs of 6 testing strategies were compared against their risks of missing pt managed as HNPCC. Methods: 185 consecutive CRCs were prospectively tested by both immunohistochemistry (IHC, for protein expressions of MLH1, MSH2, MSH6, PMS2) and PCR-based MSI. Secondary tests included MLH1 promoter methylation, BRAF mutation, and germline mutation, as appropriate. A decision tree compared the strategy of performing both IHC and MSI in all (Strategy 1) to five alternatives (Strategies 2-6, Table ). Costs were obtained from commercial list prices, Medicare reimbursement, and literature; probabilities were calculated from pt data. Incremental cost-effectiveness ratios (ICERs) were reported for each additional pt managed as HNPCC Results: 20 (10.8%) pts were identified as being managed as HNPCC. Performing IHC and MSI in all (Strategy 1) or IHC first in all followed by MSI when IHC was normal (Strategy 4) detected all 20 cases. When compared to performing IHC only (Strategy 2), Strategy 4 demonstrated an ICER of $31,821 per additional case detected, while other strategies were more costly and/or less effective (Table). Between the two strategies that detected all cases of HNPCC, Strategy 4 was less costly ($1,049 vs $1,098 per patient, Table). Conclusions: When combined with appropriate secondary and confirmatory testing, performing IHC and MSI in all or IHC in all followed by MSI when IHC were normal, both showed a zero miss rate, while the latter was slightly more cost-effective. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 4_suppl ( 2012-02-01), p. 546-546
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 546-546
    Abstract: 546 Background: The treatment standard for rectal cancer patients after neoadjuvant chemoradiotherapy (CXRT) and radical resection includes adjuvant chemotherapy (CT). The purpose of this study was to evaluate patient demographic and clinicopathologic characteristics in relation to adjuvant CT use. Methods: A retrospective cohort study of patients ≥ 65 years old with rectal cancer treated by neoadjuvant CXRT and radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007, Medicare Part A/B only) was performed. Multivariate logistic regression was used to assess CT utilization in relation to patient, tumor and treatment response characteristics. Results: Among 1344 patients who met study criteria, 748 (55.6%) received adjuvant CT with 5-fluorouracil (FU) including 189 (25.3%) who also received oxaliplatin (Ox). ypStage was the strongest determinant of both any post-operative CT (43.1% stage I, 51.3% stage II, 73.4% stage III). Other associated factors included age, comorbidity, marital status and surgery type. In addition, age, socioeconomic status, and grade were associated with Ox use. These effects persisted even after exclusion of patients with comorbidities. Conclusions: Although standard treatment guidelines for locally advanced rectal cancer include postoperative CT for all patients after neoadjuvant CXRT and radical resection, nearly 1 in 2 patients failed to receive adjuvant CT. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 544-544
    Abstract: 544 Background: The goal of this phase I trial was to determine the maximal tolerated dose (MTD) of concurrent capecitabine, bevacizumab and erlotinib with preoperative radiation therapy (RT) for rectal cancer, with a secondary objective of evaluating pathologic complete response (pCR). Methods: Eligibility criteria included patients with clinical stage II-III rectal adenocarcinoma within 12 cm from the anal verge. Exclusion criteria included uncontrolled hypertension, recent myocardial infarction or angina, coagulopathy, impaired renal function, and history of gastrointestinal perforation. Patients were treated in cohorts of 2, in 4 escalating dose levels (DL), using the continual reassessment method, as shown in the table. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: Nineteen patients were enrolled in the study: 1 withdrew early because of insurance issues and was non-evaluable. The clinical stage was T3N0 in 3, T3N1 in 13, T3N2 in 1 and T4N0 in 1 patient. No patient had grade 4-5 acute toxicity; 1 patient had grade 3 acute toxicity (hypertension, DL 2) during or within 4 weeks after RT. The MTD was not reached; the probability of dose limiting toxicity at DL 4 was 0.15. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 5 (28%), and abdominoperineal resection in 6 (33%) patients. Eight patients (44%) had pCR, and an additional 8 (44%) had ≤ 10% viable tumor in the surgical specimen. Fifteen patients (83%) had T downstaging. Three patients developed grade 3 post-operative complications (ileus, small bowel obstruction and infection). After a median follow-up of 21 months (range 9-39 months), no patient had local recurrence, but 1 patient developed distant metastasis. Conclusions: The combination of preoperative RT with concurrent capecitabine, bevacizumab and erlotinib was well tolerated. The pCR rate of 44% is promising and warrants further investigation. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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