Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy.

BACKGROUND: Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. METHODS: Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. RESULTS: The 5-year Kaplan-Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. CONCLUSION: Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective.

Ability of positron emission tomography to detect residual neck node disease in patients with head and neck squamous cell carcinoma after definitive chemoradiotherapy.

OBJECTIVE: To report our experience using the neck examination, computed tomography (CT), and positron emission tomography (PET) to clinically evaluate node-positive patients with head and neck squamous cell cancer for residual neck node disease after definitive chemoradiotherapy. DESIGN: Retrospective review of all Cleveland Clinic patients with head and neck squamous cell cancer and N2 or N3 neck node involvement at presentation who were treated with definitive concurrent chemoradiotherapy and who underwent clinical restaging after treatment using the neck examination, CT, and PET. SETTING: Tertiary care referral institution. PATIENTS: Forty-eight patients with 72 positive necks at diagnosis were followed up for a median of 20 months. MAIN OUTCOME MEASURES: Palpable nodes on examination, nodes larger than 1 cm, nodes with central necrosis on CT, or any hypermetabolic lymph nodes on PET were considered clinical evidence of residual nodal disease. The true rate of pathologic involvement was determined by histologic examination after planned neck dissection or if regional recurrence developed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 3 clinical assessment tools. RESULTS: Planned neck dissection was performed in 33 necks and was positive for residual neck node disease in 5 necks. A delayed neck dissection was performed in 5 necks and was positive in 3 necks. The positive predictive value was low for all 3 clinical assessment tools. The addition of PET did not significantly improve the negative predictive value or positive predictive value of CT and the clinical examination. CONCLUSIONS: Residual neck node disease after definitive chemoradiotherapy was infrequent and was not well predicted by PET. A positive PET finding in this setting is of little utility. Although a negative PET finding was highly predictive for control of neck disease after chemoradiotherapy, it added little to the clinical neck examination and CT.

A phase II trial of accelerated multimodality therapy for locoregionally advanced cancer of the esophagus and gastroesophageal junction: the impact of clinical heterogeneity.

OBJECTIVES: This is a report of mature results from a phase II trial of an accelerated multimodality treatment program for locoregionally advanced cancer of the esophagus and gastroesophageal junction with a focus on the impact of clinical heterogeneity on outcomes. A split course of pre- and postoperative hyperfractionated radiation therapy and concurrent chemotherapy was used in an effort to limit perioperative mortality. METHODS: Eligibility required a diagnosis of esophageal or gastroesophageal junction cancer and an esophageal ultrasound stage of at least T3, N1, or M1A. Patients received a 12-day induction course of radiation (1.5 Gy twice a dose to a dose of 30 Gy) concurrent with 4-day continuous intravenous infusions of cisplatin (20 mg/m2 per day) and 5-fluorouracil (1000 mg/m2 per day) beginning on day 1. Surgery followed in 4 to 6 weeks followed 6 to 10 weeks later by a second, identical course of chemoradiotherapy. RESULTS: From October 1999 through March 2003, 93 patients were enrolled; 96% were white, 86% male, and 83% had adenocarcinoma. Resection was possible in 83 patients (89%) with 4 (5%) perioperative deaths. With a median follow up of 50 months (range, 34-72 months), the 3-year projected overall survival rate is 27.9%, freedom from recurrence 30.5%, and distant metastatic control 32.4%. Locoregional control in resected patients is 86%. Freedom from recurrence and distant control were significantly better in patients with 1) earlier pretreatment clinical stage, 2) earlier postinduction pathologic stage, 3) squamous cell cancer, and 4) a pathologic response. CONCLUSIONS: This accelerated multimodality treatment program is feasible and perioperative mortality proved acceptable. Despite excellent locoregional control, freedom from recurrence, and overall survival proved disappointing reflecting the frequency of distant metastases. Heterogeneity in patient populations makes comparisons with similar nonrandomized experiences problematic.

Multiagent concurrent chemoradiotherapy for locoregionally advanced squamous cell head and neck cancer: mature results from a single institution.

PURPOSE: A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer. PATIENTS AND METHODS: Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease. RESULTS: With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors. CONCLUSION: Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.

Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?

BACKGROUND: The role of neck dissection (ND) after definitive chemoradiotherapy for squamous cell head and neck cancer is incompletely defined. We retrospectively reviewed 109 patients with N2-N3 disease treated with chemoradiotherapy to identify predictors of a clinical complete response in the neck (CCR-neck), pathologic complete response after ND (PCR-neck), and regional failure. METHOD: All patients were given 4-day continuous infusions of 5-fluorouracil (1000 mg/m2/d) and cisplatin (20 mg/m2/d) during the first and fourth weeks of either once daily (n = 68) or twice daily (n = 41) radiation therapy. ND was considered for all patients after completion of chemoradiotherapy and was performed in 32 of the 65 patients achieving a CCR-neck after chemoradiotherapy and in all 44 patients with residual clinical evidence of neck disease. CCR-neck, PCR-neck, and regional failure were then correlated with potential predictors, including T, N, largest lymph node size (<3 cm, > or =3 cm), primary tumor site, and radiation fractionation schedule. RESULTS: Achievement of a CCR-neck was predicted by N, N2 vs N3 (53 of 80 vs 12 of 29, p =.019) and by largest lymph node size, <3 cm vs > or =3 cm (19 of 25 vs 46 of 84, p =.06). Achievement of a PCR-neck could not be predicted by any clinical parameter. Regional failure occurred both in patients undergoing ND and those not dissected (5 of 76 vs 4 of 33, p =.33) and proved more likely only in the ND patients with residual positive pathology compared with those achieving a PCR-neck (5 of 25 vs 0 of 51, p <.001). Primary site was not a useful predictor of CCR-neck, PCR-neck, or regional failure. Most importantly, CCR-neck (vs

Preschoolers' inhibition in their home: relation to temperament.

Researchers assessed 58 preschoolers' reactions to an unfamiliar person and unfamiliar objects in their familiar home environment. Children participated in a 30-min procedure designed to elicit behavioral inhibition, including (a) a free-play period with a stranger present, (b) a structured interaction with the stranger, and (c) uncertainty-eliciting tasks. Behaviors representing the child's reactions toward the mother, stranger, and novel objects were coded. Mothers completed a temperament scale. Preschoolers exhibited behaviors indicative of inhibition toward unfamiliar social and nonsocial stimuli; behaviors remained stable across increasingly intrusive episodes. The approach/withdrawal component of temperament was related to behavioral inhibition. Individual differences in mood did not appear to be related to differences in inhibition. Parent reported temperament was related to researcher-observed behaviors.

Accelerated hyperfractionated radiation, concurrent paclitaxel/cisplatin chemotherapy and surgery for stage III non-small cell lung cancer.

The low surgical cure rate in patients with stage III non-small cell lung cancer has prompted an exploration of multimodality treatment strategies. Mature results are presented from a phase II trial of accelerated hyperfractionated radiation therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage III non-small cell lung cancer underwent induction treatment with a 96 h continuous cisplatin infusion (20 mg/m(2) per day) and a 24 h infusion of paclitaxel (175 mg/m(2)) given concurrently with accelerated hyperfractionated radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was completed in ten treatment (12 total) days. Surgical resection was scheduled 4 weeks later with a second identical course of chemoradiotherapy given 4-6 weeks post-operatively, to a total radiation dose of 60-63 Gy. Thirty-five patients had stage III(A) disease and ten had stage III(B) disease (eight with N(3) tumors). Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia <1000/mm(3) in 84% which required hospitalization for fever in 40%. There were no toxic deaths during induction. About 40 of the 45 patients (89%) were operable and 32 (71%) were resectable for cure. A pathologic response was identified in 22 patients (49%); five patients (11%) had no residual disease. Fourteen patients (31%) were downstaged to mediastinal node negativity. With a median follow-up of 60 months, the Kaplan-Meier projected 5-year overall survival was 29%; locoregional control 79%; and distant metastatic disease control 38%. The projected 5-year survival for the 14 patients downstaged to mediastinal node negativity was 50%. For the 19 patients with residual ipsilateral mediastinal node involvement at surgery it was 32%. This short-course of paclitaxel and cisplatin chemotherapy and concurrent accelerated fractionation radiation is tolerable despite significant myelosuppression. Locoregional control is excellent and survival is better than historical expectations. Patients downstaged to mediastinal node negativity have a prognosis similar to those with de novo stage I(B) and II disease. Distant metastases are the major cause of treatment failure.

Maximizing local control and organ preservation in stage IV squamous cell head and neck cancer With hyperfractionated radiation and concurrent chemotherapy.

PURPOSE: Results are reported from an aggressive chemoradiotherapy protocol for advanced squamous cell head and neck cancer. PATIENTS AND METHODS: Patients with advanced squamous cell head and neck cancer were treated with hyperfractionated radiation therapy (72 Gy at 1.2 Gy twice per day) and two courses of concurrent chemotherapy with fluorouracil (1,000 mg/m(2)/d) and cisplatin (20 mg/m(2)/d), both given as 96-hour continuous intravenous infusions during weeks 1 and 4 of radiation therapy. Primary-site resection was reserved for residual or recurrent primary-site disease after chemoradiotherapy. Neck dissection was considered for N2 or greater disease, irrespective of clinical response, and for residual or recurrent neck disease after nonoperative treatment. RESULTS: Forty-one patients with stage IV disease were treated. Toxicity was significant, with grade 3 to 4 mucositis in 98%, dysphagia in 88%, and skin reaction in 85%. Neutropenic fever requiring hospitalization occurred in 51%. Despite feeding tube placement in 35 patients (85%), the mean weight loss during chemoradiotherapy was 13.3% of initial body weight. One patient died during treatment as a result of a pulmonary embolus. At a median follow-up period of 30 months, the 3-year Kaplan-Meier projected overall survival was 59%, disease-specific survival 69%, likelihood of local control without surgical resection 91%, and local control with surgical resection 97%. The likelihood of distant disease control at 3 years was 74%, and distant metastases were present in eight of 13 patients who died. CONCLUSION: This chemoradiotherapy schedule produces considerable but manageable toxicity. Survival and organ preservation are excellent for this poor-prognosis patient cohort. Distant metastases are the most common cause of treatment failure.