Timing of radiotherapy and chemotherapy start for patients treated with definitive concurrent chemoradiation for head and neck cancer.

BACKGROUND: The ideal timing for the initiation of chemotherapy and radiation therapy (RT) in the use of definitive chemoradiation (CRT) for patients with head and neck cancer is not well established. We sought to evaluate the impact of the timing of initiating these two modalities on clinical outcomes. MATERIALS AND METHODS: Patients with squamous cell carcinoma of the head and neck who were treated using definitive chemoradiation from 2012 to 2018 were identified. Patients undergoing re-irradiation, post-op CRT, had recurrent or second primaries, or ECOG 3-4 were excluded. Outcomes including locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated and compared between subgroups of the cohort based on the timing in which chemotherapy or RT were initiated: chemotherapy first, same day start, within 24 h, or start on Monday/Tuesday/Wednesday. RESULTS: A total of 131 patients were included for analysis consisting of oropharynx (64%), larynx (22.9%), nasopharynx (6.9%), hypopharynx (3.1%), oral cavity (1.5%), and unknown primary (1.5%). Chemotherapy was administered as bolus cisplatin every 3 weeks in 40% of patients and weekly cisplatin in 60% with a median cumulative dose of 240 mg/m2. In the multivariable analysis (MVA), starting chemotherapy before RT was associated with improved LRC (HR 0.33, 95% CI: 0.11-0.99). Three-year LRC for patients starting chemotherapy first was 90.9% compared to 78.2% in those starting RT first. In the MVA, cisplatin regimen and cumulative cisplatin dose were associated with improved OS, while no factors were significantly associated with DC or PFS. CONCLUSION: Starting chemotherapy prior to radiation therapy improves LRC, but did not impact DC, PFS, or OS. Clinical outcomes were not different when stratifying by the other differences in the timing of initiating chemotherapy or RT.

Timing of chemotherapy-induced neutropenia predicts prognosis in metastatic colon cancer patients: a retrospective study in mFOLFOX6 -treated patients.

BACKGROUND: The occurrence of Chemotherapy-induced neutropenia (CIN) was reported to be a predictor of better survival in several cancers. The objective of our study is to evaluate the relationship between the timing of CIN and prognosis. METHODS: Between June 2012 and August 2014, 290 patients with confirmed metastatic colon cancer received at least one cycle of mFOLFOX6 as first-line chemotherapy were eligible for assessment as all patients group. Of the 232 received at least six cycles of mFOLFOX6 and survived 150 days after treatment were considered as landmark group. Timing of CIN was categorized into absence, early-onset and late-onset CIN groups. The end of cycle 3 was the cutoff to differentiate early-onset or late-onset. The correlation between timing of CIN with survival was analyzed by Kaplan-Meier method and Cox proportional hazards model. RESULTS: In all patients group, the median survival of patients without neutropenia, early-onset and late-onset neutropenia were 6.7, 20.7 and 12.8 months (P < 0.001). The patients with early-onset and late-onset CIN had better prognosis than CIN absence by multivariate analysis. Findings were much the same for landmark group. CONCLUSIONS: In conclusion, timing of CIN is an independent predictor of prognosis in metastatic colon cancer patients received mFOLFOX6, whereas an early-onset of CIN predicts longer survival.

Use of chemotherapy and radiofrequency ablation to treat colorectal cancer metastases: a retrospective review of The Ottawa Hospital Cancer Centre over 7 years.

BACKGROUND: Almost 40% of people diagnosed with colorectal cancer will die from their disease, most with metastatic spread. When feasible, hepatic resection offers the greatest probability of cure for isolated liver metastases, but there are barriers to curative resection. Those barriers include the extent and distribution of lesions within the liver, extrahepatic disease, comorbidities, and age. Chemotherapy is often administered before or after resection with the intention of improving disease-free and overall survival. The timing of chemotherapy (adjuvant vs. neoadjuvant vs. perioperative) for patients undergoing potentially curative hepatic resection of metastasis of colorectal cancer origin is controversial. METHODS: Colorectal cancer patients with liver metastases resected at The Ottawa Hospital between January 1, 2003, and December 31, 2009, were identified, and their clinical records were retrospectively reviewed. Patients receiving intraoperative radiofrequency ablation (rfa) as part of their management were included. Factors associated with overall and disease-free survival were evaluated. RESULTS: The 168 identified patients (57% men, 43% women) had a median age of 63 years (range: 31-84 years). After hepatectomy, 10% had positive resection margins. Intraoperative rfa was used in 25 patients (15%). Chemotherapy was administered in the neoadjuvant (19%), adjuvant (31%), or "perioperative" (both neoadjuvant and adjuvant, 50%) setting. Use or omission of intraoperative rfa was not associated with a difference in overall survival (hazard ratio: 0.99; 95% confidence interval: 0.53 to 1.84; p = 0.97). CONCLUSIONS: Compared with patients who did not receive chemotherapy, those who received chemotherapy, regardless of timing, experienced improved overall survival and disease-free survival. Use of rfa where required as an adjunct to hepatic resection appears to be effective and is not associated with worse overall survival.

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma - analysis of patient data in the prospective OVCAD study.

OBJECTIVE: Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. METHODS: Data of 191 patients with advanced serous (FIGO III-IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. RESULTS: The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus >28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08-4.66), P=0.031]. CONCLUSION: Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.

Timing of Initiation of Palliative Chemotherapy in Asymptomatic Patients with Metastatic Pancreatic Cancer: An International Expert Survey and Case-Vignette Study.

Background: The use of imaging, in general, and during follow-up after resection of pancreatic cancer, is increasing. Consequently, the number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC) is increasing. In these patients, palliative systemic therapy is the only tumor-directed treatment option; hence, it is often immediately initiated. However, delaying therapy in asymptomatic palliative patients may preserve quality of life and avoid therapy-related toxicity, but the impact on survival is unknown. This study aimed to gain insight into the current perspectives and clinical decision=making of experts regarding the timing of treatment initiation of patients with asymptomatic mPDAC. Methods: An online survey (13 questions, 9 case-vignettes) was sent to all first and last authors of published clinical trials on mPDAC over the past 10 years and medical oncologists of the Dutch Pancreatic Cancer Group. Inter-rater variability was determined using the Kappa Light test. Differences in the preferred timing of treatment initiation among countries, continents, and years of experience were analyzed using Fisher's exact test. Results: Overall, 78 of 291 (27%) medical oncologists from 15 countries responded (62% from Europe, 23% from North America, and 15% from Asia-Pacific). The majority of respondents (63%) preferred the immediate initiation of chemotherapy following diagnosis. In 3/9 case-vignettes, delayed treatment was favored in specific clinical contexts (i.e., patient with only one small lung metastasis, significant comorbidities, and higher age). A significant degree of inter-rater variability was present within 7/9 case-vignettes. The recommended timing of treatment initiation differed between continents for 2/9 case-vignettes (22%), in 7/9 (77.9%) comparing the Netherlands with other countries, and based on years of experience for 5/9 (56%). Conclusions: Although the response rate was limited, in asymptomatic patients with mPDAC, immediate treatment is most often preferred. Delaying treatment until symptoms occur is considered in patients with limited metastatic disease, more comorbidities, and higher age.

Timing of chemotherapy-induced neutropenia: the prognostic factor in advanced pancreatic cancer patients treated with gemcitabine / gemcitabine-based chemotherapy.

Chemotherapy-induced neutropenia (CIN) was reported to be a predictor of better survival in several cancers. The objective of our study is to evaluate the relationship between the timing (onset) of CIN and prognosis. Between June 2008 and June 2015, 134 patients with confirmed advanced pancreatic cancer received at least one cycle of gemcitabine / gemcitabine-based chemotherapy as first-line chemotherapy were eligible for assessment. Timing of CIN was categorized into early onset and non-early onset CIN group. The end of cycle 2 was the cutoff to differentiate early onset or non-early onset. The correlation between timing of CIN with survival was analyzed by Kaplan-Meier method and Cox proportional hazards model. Median overall survival (OS) was 8.05 months (95% CI: 5.97-10.13) for patients with early onset CIN compared with 5.82 months (95% CI: 5.00-6.63) for patients without early-onset neutropenia (P = 0.022). Multivariate analysis proved that timing of CIN was an independent prognostic factor, hazard ratios of death was 0.696 (95% CI: 0.466-0.938) for patients with early onset CIN. In conclusion, timing of CIN is an independent predictor of prognosis in patients with advanced pancreatic cancer undergoing gemcitabine / gemcitabine based chemotherapy. Early-onset CIN predicts better survival.

Effect of delay in adjuvant oxaliplatin-based chemotherapy for stage III colon cancer.

BACKGROUND: Less than 8 weeks has been recommended as the optimal time to initiate AC based on 2 meta-analyses that suggested worse survival with delayed AC. However, neither study included patients treated with an oxaliplatin-based chemotherapy. We aimed to investigate the effect of delay in initiating oxaliplatin-based chemotherapy on RFS and CSS for stage III colon cancer. PATIENTS AND METHODS: Records of patients who initiated oxaliplatin-based AC for stage III colon cancer between 2006 and 2011 at the British Columbia Cancer Agency were retrospectively reviewed. Cox proportional models were used to analyze the effect of time to AC (TTAC) on RFS and CSS. TTAC was categorized into ≤ 8 weeks (G1) and > 8 weeks (G2). RESULTS: Six hundred thirty-five patients were included (G1, n = 291; G2, n = 344). Median time from surgery to initiation of AC was 8.3 weeks. At a median follow-up of 57.9 months, 176 patients (27.7%) had disease recurrence and 118 (18.6%) had died. Five-year RFS was 70.9% (95% confidence interval [CI], 65.2-76.5) for G1 and 72.1% (95% CI, 67.2-77) for G2. Five-year CSS was 82% for G1 (95% CI, 87.09-76.91) and 82.8% for G2 (95% CI, 78.30-87.30). On multivariate analysis, delayed TTAC did not have prognostic significance on either RFS (hazard ratio [HR], 1.08; P = .609) or CSS (HR, 1.02; P = .893). CONCLUSION: In our population-based study, TTAC after stage III colon cancer resection did not have an effect on RFS or CSS. Contrary to most of the existing data, which are primarily based on 5-fluorouracil-based AC, delay of oxaliplatin-based AC beyond 8 weeks did not appear to be associated with inferior outcomes.