Radiomic Features of Primary Rectal Cancers on Baseline T
            2
            ‐Weighted MRI Are Associated With Pathologic Complete Response to Neoadjuvant Chemoradiation: A Multisite Study

597 Background: Preoperative concurrent radiation with either 5-fluorouracil (5FU) or capecitabine (CAP) is considered standard of care for T3-T4 and/or node positive rectal cancers with historical pathological complete response (pCR) rates ranging from 7-29%. There is lack of randomized data on the incorporation of bevacizumab (B) and cetuximab (C) with neoadjuvant chemoradiation (CRT). The aim of our study was to quantify pCR and adverse event rates for B-CRT and C-CRT in patients with rectal cancer. Methods: A systematic literature review using the Medline database and national meeting abstracts identified trials incorporating bevacizumab and cetuximab for neoadjuvant chemoradiation between 2000 and 2011. Pooled rates of pCR and frequency of grade 3-4 adverse events per patient with 95% confidence intervals (CI) using the adjusted Wald method, were calculated. Results: Out of 24 trials identified, 15 trials with a total of 457 (range 8-61) patients incorporated B-CRT. Five studies used 5FU, ten used CAP. A third chemotherapeutic agent was also included in 7 trials of B-CRT. There were 9 trials incorporating C-CRT with a total of 332 (range 20-50) patients. Two studies used 5FU, 7 used CAP, while four studies also included a third therapeutic agent. The pooled pCR rate for B-CRT of 20.8% (95% CI 17.3-24.8), was significantly higher than the 9.6% (95%CI 6.92-13.2) pCR rate for C-CRT (p < 0.001). The rate of grade 3-4 adverse events was significantly lower for B-CRT at 0.38 per patient studied (95% CI 0.34-0.43) compared to C-CRT at 0.55 per patient (95%CI 0.49-0.60) (p<0.001). Surgery was performed in 92% of B-CRT and 94% of C-CRT patients. Conclusions: The addition of either B or C to conventional neoadjuvant CRT does not appear to yield higher pCR rates than those reported with conventional CRT alone. There is insufficient evidence to support routine use of novel agents in this treatment strategy for rectal cancer. Interestingly, although surgical rates are high in both groups, C-CRT has significantly lower rates of pathologic complete response and significantly higher rates of toxicity than B-CRT.

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Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes

The American Surgeon ◽

10.1177/0003134820972083 ◽

2020 ◽

pp. 000313482097208

Author(s):

Christof Kaltenmeier ◽

Alison Althans ◽

Maria Mascara ◽

Ibrahim Nassour ◽

Sidrah Khan ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Therapy ◽

Gastric Adenocarcinoma ◽

Survival Rates ◽

Pathologic Complete Response ◽

Tumor Grade ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

National Cancer Database ◽

The Impact

Introduction With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. Methods We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. Results The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. Conclusion In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

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Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Clinical and Translational Radiation Oncology ◽

10.1016/j.ctro.2017.04.004 ◽

2017 ◽

Vol 4 ◽

pp. 8-14 ◽

Cited By ~ 19

Author(s):

Gabriella Macchia ◽

Maria Antonietta Gambacorta ◽

Carlotta Masciocchi ◽

Giuditta Chiloiro ◽

Giovanna Mantello ◽

...

Keyword(s):

Rectal Cancer ◽

Population Study ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Time To Surgery

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High complete response (CR) rate in patients (pts) with esophageal carcinoma (EC) undergoing neoadjuvant combination of docetaxel and cisplatin (DC) ± cetuximab(DCE) chemoradiation therapy—a retrospective analysis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15093 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15093-15093

Author(s):

T. J. Fillos ◽

P. Hentschel ◽

K. Watkins ◽

M. S. Karpeh ◽

A. Meek ◽

...

Keyword(s):

Objective Response ◽

Pathologic Complete Response ◽

Stage Iv ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

High Rate ◽

Phase Iii ◽

Weekly Docetaxel ◽

Stage Iv Disease ◽

Grade 3

15093 Background: EC is a highly lethal disease with 5 year survival less than 15%. Surgery offers a chance for cure in early disease. Still, fewer than 20% of pts treated with surgery alone are alive at 5 years. Neoadjuvant chemoradiation offers the theoretical advantage of increasing R0 resections and reducing early local and distal metastases which may translate into improved survival. Several clinical trials have resulted in pathologic complete response (pCR) rates of 20–30%. Methods: Newly diagnosed pts with EC Stage 2A (T3) to 4 received weekly Docetaxel (D)25–30mg/m2 and Cisplatin (C)25–30mg/m2.for 6–8 weeks concurrently with radiation, 5040 cGy in 28 fractions. Cetuximab (E) 200mg/m2 was added after it became accepted treatment in head and neck cancers. Pts were scheduled 4 - 6 weeks later for surgery followed by the same chemotherapy for total of 16 weeks of treatment. Pts were assessed for time to progression, overall survival and toxicities. Results: Fifteen pts treated in 2005–6 underwent IRB approved evaluation; 11 male and 4 female, median age of 62(range 44–78) . Four had squamous cell (SCC) and 11 adenocarcinomas. Nine pts had Stage II, 4 pts stage III and 2 pts stage IV disease. Seven pts underwent surgery, all R0 resections. Four of them had pCR, one pPR (downstaged from T3 to T1) and two pts had stable disease. An additional 3 pts had radiological and endoscopic proven CR (medically not surgical candidates) for an objective response (CR+PR) in 8 out of 15 pts (3 SCC and 5 adenoca). Five out of 9 receiving DC had an objective response while 3 of 6 receiving DCE responded. Five pts progressed prior to surgery. Grade 3/4 neutropenia occurred in 2, nausea in 3, and 1 pt experienced Grade 3 dehydration. Four patients required dose reductions by 20%. Six patients had one cycle and 2 had 3 cycles delayed by one week each. Conclusions: Neoadjuvant chemoradiation treatment with weekly Docetaxel and Cisplatin ± Cetuximab is tolerable with high rate of CRs. There was no observed difference in response with the addition of cetuximab. A Phase III study is suggested. No significant financial relationships to disclose.

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Initial experience using percutaneous irreversible electroporation (IRE) in the treatment of locally advanced pancreatic adenocarcinoma (LAPC) with vascular encasement.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.291 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 291-291 ◽

Cited By ~ 1

Author(s):

Peter Joel Hosein ◽

Katuska J Barbery ◽

Evelyn Perez-Rojas ◽

Tatiana Froud ◽

Caio Max S. Rocha Lima ◽

...

Keyword(s):

Neoadjuvant Therapy ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Pancreatic Tumors ◽

Percutaneous Ablation ◽

Initial Experience

291 Background: Neoadjuvant chemoradiation therapy can convert some patients (pts) with borderline or unresectable LAPC to resectability. Persistent vascular encasement after neoadjuvant therapy usually contraindicates resection. IRE using the Nanoknife is more versatile than other ablative modalities in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of pts referred for IRE for LAPC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was safety. Secondary endpoints included survival and resection rate after the procedure. Results: Between 12/2010 and 8/2011, 8 pts with biopsy-proven PC underwent percutaneous ablation of pancreatic tumors using IRE. The median age was 53 years (range 51-72), the median time from diagnosis to IRE was 8.8 months (range 2.4-29.2) and the median tumor size treated was 2.8cm (range 2.5-6.8). All pts had prior chemotherapy and 7 had prior radiation, with a median of 2 lines of prior therapies (range 1-4). Two pts went to surgery after IRE after 4 and 5 months respectively. Both had margin-negative (R0) resections and one had a pathologic complete response. Both remain disease-free at 1 and 5 months after resection respectively. Among the 6 remaining pts, 2 were lost to follow-up, one had progressive disease after 3 months and 3 remain under follow-up to determine resectability. One of these 3 pts had a negative follow-up PET scan and surgery is planned. The procedure was complicated by a spontaneous pneumothorax during anesthesia in one patient, and another developed pancreatitis; both recovered completely. Conclusions: Percutaneous ablation of pancreatic tumors appears to be feasible and safe using the IRE modality. In our initial experience, 2 out of 8 pts with unresectable LAPC due to persistent vascular encasement after neoadjuvant therapy achieved a margin-negative resection after IRE. One had a pathological complete response. A prospective neoadjuvant trial in LAPC incorporating IRE is planned.

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Effect of postoperative chemotherapy (CT) on survival in patients (pts) with resected rectal cancer who received neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14535 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14535-e14535

Author(s):

Christina Sing-Ying Wu ◽

Lai Wei ◽

Katherine Glass ◽

John Wilson ◽

Sherif Abdel-Misih ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Benefit ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Wilcoxon Test ◽

Stage Ii ◽

Categorical Variables ◽

Rank Test ◽

Significant Difference

e14535 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August, 2005 to July, 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19% N1 or N2, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]

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Assessment of macroscopic features in relation to tumor response to neoadjuvant chemoradiation therapy in rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.507 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 507-507

Author(s):

Amanda Kathleen Arrington ◽

Julio Garcia-Aguilar ◽

Marjun Philip Duldulao ◽

Carrie Luu ◽

Julian Sanchez ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Response ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Chemoradiation Therapy ◽

Oncologic Outcomes ◽

Neoadjuvant Chemoradiation Therapy ◽

Pathologic Features

507 Background: Several studies show locally advanced rectal cancer patients with clinical complete response (cCR) have comparable oncologic outcomes to pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (NCRT). Thus, total mesorectal excision (TME) could potentially be avoided. Our objective was to validate macroscopic features of cCR. Methods: 164 patients with stage II/III rectal cancer were previously enrolled in a phase II trial and treated by NCRT and TME. Tumor response in the surgical specimens was assessed according to AJCC guidelines. A pCR was defined as absence of viable tumor cells. Gross macroscopic features by the pathologist were tabulated and our cohort was applied to previously published cCR criteria. Results: 25.0% (n = 41) had pCR; 75.0% (n = 123) had non-pCR. Descriptors were condensed into 14 macroscopic features by combining terms and excluding those rarely mentioned. Several reports affirm that scarring signifies cCR, while others suggest that fibrosis, edema, ulceration and nonpalpable tumor to be consistent with cCR. In our study, scarring was found in 6.1% of patients, 16.7% of which had pCR. We found that hyperemia, scarring, flat, smooth, and tan-pink mucosa were significantly associated with pCR (p < 0.05). In contrast, a firm lesion and ulceration were frequently observed in patients with non-pCR (p = 0.02 and 0.05 respectively). Conclusions: Our study suggests that macroscopic pathologic features do correlate with pCR. Although cCR has comparable oncologic outcomes as pCR with favorable outcomes, standard criteria of cCR should first be defined so NCRT patients can safely be selected for observation only. [Table: see text]

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Survival differences in patients (pts) with resected rectal cancer who received neoadjuvant therapy with or without postoperative chemotherapy (CT).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.518 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 518-518

Author(s):

Christina Sing-Ying Wu ◽

Lai Wei ◽

Katherine Glass ◽

John Wilson ◽

Sherif Abdel-Misih ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Benefit ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Wilcoxon Test ◽

Stage Ii ◽

Categorical Variables ◽

Rank Test ◽

Significant Difference

518 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August 2005 to July 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two pt groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19%, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]

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Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps816 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS816-TPS816

Author(s):

Jianwei Zhang ◽

Yue Cai ◽

Huabin Hu ◽

Jian Xiao ◽

Dianke Chen ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii Study ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Neoadjuvant Chemoradiation ◽

Chemoradiation Therapy ◽

Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

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