Cristina P. Rodriguez

Randomized phase III study of 2 cisplatin-based chemoradiation regimens in locally advanced head and neck squamous cell carcinoma: Impact of changing disease epidemiology on contemporary trial design

Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens.

Genomic medicine and targeted therapy for solid tumors

A marked paradigm shift in cancer therapy has occurred over the past 20 years. Systemic treatment has evolved from nonspecific cytotoxic chemotherapy to targeting cancer‐associated pathways, profoundly changing treatment approaches in the metastatic and adjuvant settings. This review will highlight some of the major clinical advances in targeted cancer therapy in select epithelial malignancies made possible by the understanding of the molecular mechanisms driving tumor growth through genomic methods. J. Surg. Oncol. 2015 111:38–42.

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.

NCCN guidelines® insights: Head and neck cancers, version 1.2018 featured updates to the NCCN guidelines

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma

Purpose: The WEE1 tyrosine kinase regulates G2–M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. Thus, a need arises to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel. Patients and Methods: We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with stage III/IVB HNSCC with borderline-resectable or -unresectable disease, but who were candidates for definitive chemoradiation. Escalating AZD1775 was administered orally twice a day over 2.5 days on the first week, then in combination with fixed cisplatin (25 mg/m2) and docetaxel (35 mg/m2) for 3 additional weeks. The primary outcome measure was adverse events to establish MTD. Secondary measures included response rates, pharmacokinetics (PK), pharmacodynamics, and genomic data. Results: The MTD for AZD1775 was established at 150 mg orally twice per day for 2.5 days. RECISTv1.1 responses were seen in 5 of 10 patients; histologic adjustment revealed three additional responders. The only drug-limiting toxicity was grade 3 diarrhea. The PK C8hr target of 240 nmol/L was achieved on day 4 at all three doses tested. Pharmacodynamic analysis revealed a reduction in pY15-Cdk, and increases in γH2AX, CC3, and RPA32/RPA2 were noted in responders versus nonresponders. Conclusions: The triplet combination of AZD1775, cisplatin, and docetaxel is safe and tolerable. Preliminary results show promising antitumor efficacy in advanced HNSCC, meriting further investigation at the recommended phase II dose. Clin Cancer Res; 24(12); 2740–8. ©2018 AACR.

Salivary Gland Malignancies.

Salivary gland malignant tumors represent a diverse group of neoplasms. Their low incidence makes research studies challenging, with most therapeutic recommendations based on case reviews, single-arm trials, or small randomized trials. The standard of care for localized disease is surgical resection. Radiotherapy is the preferred local therapy when surgery is not possible or if there is significant morbidity. When symptomatic metastatic disease develops, systemic therapy is considered. Recent trial accrual success with a cooperative group, treatments based on defined molecular targets, and the development of immunotherapies all hold promise in improving the care of patients with these tumors.

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.

Predictors of outcome with cetuximab and paclitaxel for head and neck squamous cell carcinoma

Identify predictors of outcome in patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with weekly cetuximab and paclitaxel (CP).

Concurrent cetuximab and postoperative radiation in resected high-risk squamous cell carcinomas of the head and neck: A single-institution experience.

Postoperative cisplatin and radiation is the standard of care for high‐risk squamous cell carcinoma of the head and neck (SCCHN). We have used cetuximab and radiation in the postoperative setting for patients deemed poor candidates for cisplatin.

Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy

Objective To evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy. Study Design Retrospective cohort study. Setting Tertiary care medical center. Subjects and Methods Patients who underwent TORS at the University of Washington from 2010 to 2017 (n = 150) were identified. All patients who were diagnosed with tonsillar carcinoma following a nononcologic tonsillectomy and subsequently underwent TORS radical tonsillectomy were included (n = 14). Tumor stage–matched subjects (n = 44) were included who did not undergo standard tonsillectomy prior to TORS. Our primary outcome was final margin status. Secondary outcomes were presence of residual tumor, receipt and dose of postoperative adjuvant therapy, disease-free survival (DFS), and disease-specific survival. Patients with <6 months of follow-up following definitive treatment were excluded from survival analyses. Results Final margin status was clear in all subjects. Residual tumor was not identified in 13 of 14 (92.9%) prior-tonsillectomy subjects following TORS radical tonsillectomy. Seven of 14 (50%) prior-tonsillectomy subjects and 12 of 44 (27.3%) TORS-matched subjects did not require adjuvant therapy due to favorable pathology. Among subjects who received post-TORS radiation therapy (RT) at our institution, RT dose reduction was achieved in 3 of 4 (75%) prior-tonsillectomy subjects and 21 of 24 (87.5%) TORS-matched subjects. Ten of 14 (71.4%) prior-tonsillectomy subjects and 31 of 44 (70.5%) TORS-matched subjects avoided post-TORS chemotherapy. DFS was not significantly different (P = .87) between prior-tonsillectomy and TORS-matched groups, and no subjects died of related disease. Conclusions Patients diagnosed with tonsillar carcinoma following a prior nononcologic standard palatine tonsillectomy are suitable candidates for revision surgery with TORS radical tonsillectomy.