Early Versus Late Recurrence in Rectal Cancer: Does Timing Matter?

BACKGROUND: The definition of early recurrence (ER) in rectal cancer is unclear, and the association of ER with post-recurrence survival (PRS) is poorly described. We therefore sought to identify if time to recurrence (TTR) is associated with PRS. METHODS: We reviewed all curative-intent resections of nonmetastatic rectal cancer from 2003 to 2018 in our institutional registry within an NCI-Designated Comprehensive Cancer Center. Clinicopathologic data at diagnosis and first recurrence were collected and analyzed. ER was pre-specified at < 24 months and late recurrence (LR) at ≥ 24 months. PRS was evaluated by the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: At a median follow-up of 53 months, 61 out of 548 (11.1%) patients undergoing resection experienced recurrence. Median TTR was 14 months (IQR 10-18) with 45 of 61 patients (74%) classified as ER. There were no significant baseline differences between patients with ER and LR. Most recurrences were isolated to the liver (26%) or lung (31%), and 16% were locoregional. ER was not associated with worse PRS compared to LR (P > 0.99). On multivariable analysis, detection of recurrence via workup for symptoms, CEA > 10 ng/mL at recurrence, and site of recurrence were independently associated with PRS. CONCLUSION: ER is not associated with PRS in patients with resected rectal cancer. Symptomatic recurrences and those accompanied by CEA elevations are associated with worse PRS, while metastatic disease confined to the liver or lung is associated with improved PRS. Attention should be directed away from TTR and instead toward determining therapy for patients with treatable oligometastatic disease.

Effect of Time to Surgery of Colorectal Liver Metastases on Survival.

PURPOSE: Resection of liver-only colorectal liver metastases (CRLM) with perioperative chemotherapy is potentially curative. Specific primary tumor and liver metastasis characteristics have been validated to estimate the risk of recurrence. We hypothesize that the time interval from diagnosis of CRLM to surgery, or time to surgery (TTS), is clinically prognostic. METHODS: Patients from a prospectively maintained institutional database at a Comprehensive Cancer Center from May 2003 to January 2018 were reviewed. Clinicopathologic, perioperative treatment, and TTS data were collected. TTS was categorized into short (< 3 months), intermediate (3-6 months), and long (> 6 months) intervals. RESULTS: Two hundred eighty-one patients were identified. While overall survival (OS) was similar across TTS, postoperative overall survival (postoperative OS) of long TTS was associated with worse survival, 44 months (95% CI, 34-52) compared to short TTS, 59 months (95% CI, 43-79), and intermediate TTS, 63 months (95% CI, 52-108), both p < 0.01. With regard to long-term OS, intermediate TTS had 5-year OS of 59% and 8-year OS of 43% compared to long TTS (5-year OS 53% and 8-year OS 18%) and short TTS (5-year OS 54% and 8-year OS 29%). Long TTS was negatively associated with postoperative OS on multivariate analysis (HR 1.6, p < 0.01) when adjusting for resection margin, CRLM size, age, and use of postoperative chemotherapy. CONCLUSION: Short and intermediate TTS had similar survival although patients with intermediate TTS may have better odds of long-term OS. While long TTS was associated with worse survival, likely due to higher disease burden, long-term survivors were still observed.

Estimation of US patients with cancer who may respond to cytotoxic chemotherapy.

AIMS PATIENTS & METHODS: In this retrospective review, we sought to estimate the proportion of patients in the USA with advanced or metastatic cancer who are eligible for and may respond to recommended first-line cytotoxic chemotherapy based on National Comprehensive Cancer Network treatment guidelines. RESULTS: Among 609,640 patients, we estimate 479,823 (78.7%, 95% CI: 78.6-78.8%) may be eligible for cytotoxic chemotherapy while 189,159 out of 609,640 patients (31.0%, 95% CI: 30.9-31.1%) may have achieved treatment response. The average objective response rate from these regimens was 48.6% (range 9.2 to 90.6%). CONCLUSION: Given the large role of cytotoxic agents in cancer, drug development in this space may remain of interest in specific cancer types, and regulatory approval of novel oncology drugs may justify head-to-head comparisons against cytotoxic regimens.

pAKT Expression and Response to Sorafenib in Differentiated Thyroid Cancer.

Sorafenib has an antitumor activity in patients with radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC). Prior research has implicated signaling through the MAPK and AKT/PI3K pathways in the progression of DTC. To assess whether the activity of these pathways is predictive of response to sorafenib, we retrospectively studied molecular tumor markers from these two pathways from a phase 2 study of sorafenib in RAIR-DTC. Tumor samples from 40 of 53 DTC subjects obtained prior to initiation of sorafenib were immunostained with DAB-labeled antibodies to phospho-AKT (pAKT), phospho-ERK (pERK), and phospho-S6 (pS6). BRAFV600E genetic mutation analysis was performed on all samples. Expression levels and mutational status were compared to response and progression-free survival (PFS) for each patient. Low tumor expression of nuclear pAKT was associated with partial response to sorafenib (p < 0.01). Patients with nuclear pAKT expression that was below the median for our sample were more than three times as likely to have a partial response as patients with equal to or above median expression. There was no correlation between tumor expression of nuclear pERK or pS6 and response. Endothelial cell and pericyte expression of pERK, pAKT, and pS6 were not predictive of response. There was no correlation between BRAFV600E mutation status and partial response. No correlation was observed between either the expression of pAKT, pERK, or pS6, or the presence of the BRAFV600E mutation, and PFS. In conclusion, lower tumor expression of nuclear pAKT was associated with higher rate of response to sorafenib. This observation justifies evaluation of combination therapy with sorafenib and an inhibitor of the PI3K/AKT signaling pathway in RAIR-DTC.

Comparison of cancer care and outcomes between a public safety-net hospital and a private cancer center.

We compared the cancer outcomes and care-associated service defects between Jackson Memorial Hospital (ABC), a large public safety-net hospital, and Sylvester Comprehensive Cancer Center (XYZ), a private not-for-profit cancer center in patients with stage II-III colorectal cancer (CC) who received adjuvant chemotherapy (AC) and in patients with diffuse large B cell lymphoma (DLBCL). Colorectal cancer patients treated at ABC were more likely to have undergone urgent surgery. While in the CC cohort, three-year overall survival and relapse-free survival rates were significantly higher among patients treated at XYZ compared with those treated at ABC, there was no significant difference between patients treated for DLBCL in the two hospitals. Colorectal cancer patients treated at ABC were more likely to have undergone urgent surgery, to have delays before surgery or during chemotherapy, and to experience a system/patient-related service defect; whereas were less likely to complete a full course of AC.