Joanna Bodmann

A phase II trial of induction epirubicin, oxaliplatin, and fluorouracil, followed by surgery and postoperative concurrent cisplatin and fluorouracil chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction

Introduction: Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy. Methods: Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m2/d, oxaliplatin 130 mg/m2/d, and fluorouracil 200 mg/m2/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m2/d) and fluorouracil (1000 mg/m2/d) during weeks 1 and 4 of radiotherapy. Results: Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control. Conclusions: Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.

The relationship between pathologic nodal disease and residual tumor viability after induction chemotherapy in patients with locally advanced esophageal adenocarcinoma receiving a tri-modality regimen

BACKGROUNDnA complete pathologic response to induction chemo-radiotherapy (CRT) has been identified as a favorable prognostic factor for patients with loco-regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastro-esophageal junction (E/GEJ). Nodal involvement at the time of surgery has been found to be prognostically unfavorable. Less is known, however, about the prognostic import of less than complete pathologic regression and its relationship to residual nodal disease after induction chemotherapy.nnnMETHODSnBetween February 2008 and January 2012, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3-T4 or N1 or M1a (AJCC 6(th)). Induction chemotherapy with epirubicin 50 mg/m(2) d1, oxaliplatin 130 mg/m(2) d1, and fluorouracil 200 mg/m(2)/day continuous infusion for 3 weeks, was given every 21 days for three courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy at 1.8-2.0 Gy/d and two courses of cisplatin (20 mg/m(2)/d) and fluorouracil (1,000 mg/m(2)/d) over 4 days during weeks 1 and 4 of radiotherapy. Residual viability (RV) was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring.nnnRESULTSnOf the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier projected 3-year overall survival (OS) for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (P<0.001). The Kaplan-Meier projected 3-year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) residual tumor viability was 67%, 42%, and 17% respectively (P=0.004). On multivariable analysis (MVA), both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3-year OS 85% (0-25% viable) vs. 51% (>25% viable), P=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3-year OS 20% (0-25% viable) vs. 21% (>25% viable), P=0.55].nnnCONCLUSIONSnRV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of residual tumor viability.

Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: A retrospective analysis of two clinical trials

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000u2009mg/m(2) /day) and cisplatin (20u2009mg/m(2) /day) as continuous infusions over days 1-4 along with 30u2009Gy radiation at 1.5u2009Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250u2009mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.

Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes.

PurposePreoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted.MethodsBetween 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50xa0mg/m2 d1, oxaliplatin 130xa0mg/m2 d1, and fluorouracil 200xa0mg/m2/day continuous infusion for 3xa0weeks, was given every 21xa0days for 3xa0cycles and was followed by surgical resection. Adjuvant CRT consisted of 50–55xa0Gy @ 1.8–2.0xa0Gy/day and 2xa0cycles of cisplatin (20xa0mg/m2/day) and fluorouracil (1000xa0mg/m2/day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy.ResultsPersistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43–8.43), pxa0=xa00.006], recurrence free survival [HR 3.04 (1.34–6.92), pxa0=xa00.008], and overall survival [HR 3.31 (1.43–7.66), pxa0=xa00.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (pxa0=xa00.048) and N descriptor (pN) (pxa0=xa00.002), a greater median number of involved lymph nodes (3 v 1, pxa0=xa00.003), and greater residual tumor viability (pxa0=xa00.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease.ConclusionsPersistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.

Measuring impact of survivorship care plans on head and neck cancer patients.

73 Background: At our institution, patients who have completed treatment for a locoregionally confined head and neck cancer are followed in a multidisciplinary head and neck survivorship clinic initiated by the administration of a formal, patient specific survivorship care plan (SCP). We sought to assess the impact of these SCP visits on patient understanding of their disease, its treatment, and potential late effects and follow up plans.nnnMETHODSnAn IRB approved survey was administered by an uninvolved third party, to an unselected sequential series of head and neck cancer survivorship patients at the time of a regularly scheduled follow up visit. The survey focused on the knowledge recalled from the SCP, and whether this changed over time. We analyzed two cohorts of patients, based on whether the SCP had been given to them within the last 18 months or not.nnnRESULTSnPreliminary results from the first 20 patients surveyed are presented. These patients received their SCP 3-27 months before being surveyed. Primary tumor sites included oropharynx (16) and larynx (4) and most patients had been treated with intensity modulated radiation therapy (19) and concurrent cisplatin (11).nnnCONCLUSIONSnAlthough patients recall about receiving a formal SCP appeared to diminish over time, the information provided by this SCP plan and subsequent survivorship visits was retained. Whether this reflected the SCP itself, or the reinforcement of continued close follow up survivorship visits cannot be determined, but merits further investigation. [Table: see text].

Gefitinib in definitive management of esophageal or gastroesophageal junction cancer

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000u2009mg/m(2) /day) and cisplatin (20u2009mg/m(2) /day) as continuous infusions over days 1-4 along with 30u2009Gy radiation at 1.5u2009Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250u2009mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.

Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials: Gefitinib in esophageal/GEJ cancer

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000u2009mg/m(2) /day) and cisplatin (20u2009mg/m(2) /day) as continuous infusions over days 1-4 along with 30u2009Gy radiation at 1.5u2009Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250u2009mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.