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Summary Background We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m 2 during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70–72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. Findings Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47–72) in the chemoradiotherapy group and 51% (40–62) in the radiotherapy plus panitumumab group. The most frequent grade 3–4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. Interpretation Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III–IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. Funding Amgen.

To describe a surgical technique of en bloc resection of lacrimal sac tumors by the shared expertise of 2 specialists to achieve optimal tumor margin clearance and the simultaneous reconstruction of the bony defect to preserve ocular functions and cosmesis.All patients who had resection of malignant nasolacrimal drainage system tumors using the combined technique and posttreatment protocol between 1997 and 2011 were studied in this retrospective, noncomparative, interventional case series. A combined medial maxillectomy and medial orbitotomy for en bloc resection of the lacrimal sac tumor was followed by reconstruction with a tailored contoured titanium mesh to support the globe and eyelid. Disease relapse, disease survival, ocular functions (vision loss, motility, globe dystopia, and diplopia), and cosmesis (medial canthal tendon dystopia and eyelid retraction) were documented.Fourteen patients with malignant lacrimal sac tumors underwent en bloc resection. Postoperative radiation was ultimately administered to 9 patients. All patients but one were alive at last follow up. Tumor recurred locally in 2 patients with a regional recurrence in a third patient. Complications from radiation therapy included skin breakdown over the mesh (9/14 patients) with nasocutaneous fistula, medial canthal tendon dystopia (2/14 patients), and corneal perforation in a patient with recurrent disease. Despite removal of the tear drainage system, only 7 of 14 patients reported epiphora. None of the patients developed diplopia after resection and radiation therapy.The combined sinus-orbit approach is an effective method of managing lacrimal sac tumors to achieve optimal tumor clearance from the orbit and nasal cavity. Simultaneous reconstruction of the bony defect with a contoured titanium mesh provides a fixation anchor for the medial canthal tendon and globe support and serves as a supporting platform for the lower eyelid and cheek to minimize midface collapse. Postoperative radiation is associated with skin flap breakdown and nasocutaneous fistula formation.

Chronic lymphocytic leukemia (CLL) is a common malignancy which may coexist with other primary cancers. CLL is rarely the cause of solitary bone lesions; such lesions in the context of CLL are believed to result from either Richter’s transformation or metastasis from another primary malignancy. Renal cell carcinoma (RCC), on the other hand, is a malignancy which frequently metastasizes to bone and may cause an osteolytic solitary bone lesion. The origin of a solitary bone lesion in a patient with multiple potential primary malignancies has prognostic implications and affects treatment protocol, and as such must be diagnosed accurately. We describe a patient with CLL and a history of RCC who is found to have an incidental solitary bone lesion of the T11 vertebra. After two separate CT-guided biopsies revealed various lymphoid cell predominance and no evidence of RCC, treatment with low dose external beam radiation therapy (EBRT) was employed. Post-therapy MRI showed further propagation of the lesion. Surgical corpectomy was subsequently performed and postoperative pathology of the lesion was consistent with RCC. The patient was treated with bisphosphonates and a higher dose of EBRT. Our case illustrates the importance of surgical excisional biopsy for accurately diagnosing the primary source metastatic to the bone in a patient with CLL and another potential primary cancer.

Introduction In 2003, consolidation docetaxel was a promising concept for unresectable stage IIIA/B nonsmall cell lung cancer (NSCLC). To test the hypothesis that chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel would be feasible and clinically active, we conducted a phase II study. Methods Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m 2 ) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks. Concurrent radiotherapy was administered more than 7 weeks to a total dose of 63 Gy in 35 fractions. Consolidation docetaxel (75 mg/m 2 ) was administered every 3 weeks for 3 doses 4 weeks after chemoradiotherapy. The primary end point was objective response rate by RECIST. Results Complete responses occurred in 4 patients and partial responses occurred in 14, for an objective response rate of 56.3% (95% confidence interval [CI], 37.7-73.6%). Median progression-free survival was 6.5 months (95% CI, 4.6-13.5); median duration of survival was 14.8 months (95% CI, 6.9-27.3). The most common hematologic toxicity was leukopenia, which were grade 3 or 4 in 16 patients (50%). Radiation pneumonitis (grade ≥2) occurred in 13 of 31 treated patients (42%). Conclusions These findings suggested that concurrent chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel is clinically active based on median survival in patients with unresectable stage III NSCLC; however, the 42% incidence of clinical radiation pneumonitis was unexpected and warrants further investigation to determine the mechanism and preventive strategies.

Background. Our aim was to determine whether percutaneous endoscopic gastrostomy (PEG) dependence was significantly different between 2 prospective trials with different radiation fractionation schemes. Methods. Stage III or IV locally advanced head and neck squamous cell carcinomas arising from the oral cavity, hypopharynx, oropharynx, nasopharynx, paranasal sinuses, or larynx were treated using hyperfractionation (A-3 protocol) or accelerated fractionation (A-4 protocol) with chemotherapy. Amifostine was administered 15 to 30 minutes preradiation, at a dose of 500 mg/day in both protocols. It was given as an infusion over 5 to 7 minutes (A-3 protocol) or subcutaneously (A-4 protocol). Data regarding PEG placement and removal were collected prospectively. Results. Thirty-five evaluable A-3 protocol patients, 14 evaluable A-4 protocol patients, and 6 patients treated per A-4 protocol guidelines, but without amifostine as they refused the medication, were included in the analysis. Pretreatment characteristics, such as sex, age, race, T classification, N classification, American Joint Committee on Cancer (AJCC) stage, were compared between the 2 groups of patients. The only significant difference between the 2 groups was AJCC stage. Thirty-five A-3 patients and 20 A-4 patients had overall survivals of 88% versus 80%, 82% versus 75%, and 66% versus 67.5% at 1, 2, and 3 years, respectively (p = .958). With regard to PEG dependence, no significant differences were seen between the 2 groups at 6, 12, or 18 months. Conclusion. PEG dependence was not significantly different between the 2 study groups. Type of altered fractionation scheme may not influence PEG dependence in patients treated with similar protocols. Future randomized studies are needed to confirm these findings. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Purpose To describe the University of Miami experience in the treatment of small cell carcinoma of the head and neck. Methods and Materials A total of 12 patients with nonmetastatic small cell carcinoma of the head and neck were treated between April 1987 and September 2007. Radiotherapy was the primary local treatment modality for 8 patients. Results Of the 12 patients, 8 had died after a median follow-up of 13 months. The 4 patients who were alive were followed for a median of 14 months. The Kaplan-Meier estimate of the proportion of small cell head-and-neck cancer patients surviving to 1 and 2 years was 63% and 26%, respectively. The percentage of patients remaining disease free at 1 and 2 years was 71% and 44%, respectively. The patients with tonsil/parotid gland cancer had significantly greater disease-specific survival compared with the other patients. The median survival time was 30 months in the tonsil/parotid group compared with 15.2 months in the other group (patients with small cell carcinoma of the sinonasal cavity, nasopharynx, and larynx). A total of 4 patients developed recurrence, 3 of whom had a distant failure component. The treatment modality was not associated with a difference in disease-specific survival. The 1-year disease-specific survival rate was 73% in the radiotherapy or radiotherapy/chemotherapy group compared with 67% in the other group. Conclusion Radiotherapy with or without chemotherapy is a reasonable alternative to surgery for patients with small cell carcinoma of the head and neck. Patients with tonsillar or parotid small cell carcinomas did better than other sites. More aggressive treatment might be warranted for patients with sinonasal carcinoma. The outcome, however, continues to be suboptimal, and more effective therapy is needed because most patients had a component of local and distant failure.