Purpose: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN). Experimental Design: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43) and dose-escalating (106, 106, 106, 106 pfu/mL for cohort 1; 106, 107, 107, 107 for cohort 2; 106, 108, 108, 108 for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored. Results: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months). Conclusions: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 106, 108, 108, 108. Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN. Clin Cancer Res; 16(15); 4005–15. ©2010 AACR.

Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m À2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P ¼ 0.0001) for GLUT1 and 0.74 (Po0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.

The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Although much commoner in the eastern hemisphere, with an age-standardised incidence rate of 0.39 per 100 000 population, cancers of the nasopharynx form one of the rarer subsites in the head and neck.1 This paper provides recommendations on the work up and management of nasopharyngeal cancer based on the existing evidence base for this condition.Recommendations• Patients with nasopharyngeal carcinoma (NPC) should be assessed with rigid and fibre-optic nasendoscopy. (R)• Nasopharyngeal biopsies should be preferably carried out endoscopically. (R)• Multislice computed tomographic (CT) scan of head, neck and chest should be carried out in all patients and magnetic resonance imaging (MRI) where appropriate to optimise staging. (R)• Radiotherapy (RT) is the mainstay for the radical treatment for NPC. (R)• Concurrent chemoradiotherapy offers significant improvement in overall survival in stage III and IV diseases. (R)• Surgery should only be used to obtain tissue for diagnosis and to deal with otitis media with effusion. (R)• Radiation therapy is the treatment of choice for stage I and II disease. (R)• Intensity modulated radiation therapy techniques should be employed. (R)• Concurrent chemotherapy with radiation therapy is the treatment of choice for stage III and IV disease. (R)• Patients with NPC should be followed-up and assessed with rigid and/or fibre-optic nasendoscopy. (G)• Positron emission tomography–computed tomography (PET–CT), CT or MRI scan should be carried out at three months from completion of treatment to assess response. (R)• Multislice CT scan of head, neck and chest should be carried out in all patients and MRI scan whenever possible and specially in advanced cases with suspected recurrence. (R)• Surgery in form of nasopharyngectomy should be considered as a first line treatment of residual or recurrent disease at the primary site. (R)• Neck dissection remains the treatment of choice for residual or metastatic neck disease whenever possible. (R)• Re-irradiation should be considered as a second line of treatment in recurrent disease. (R)

We report the use of stereotactic radiosurgery delivered through an adapted linear accelerator [stereotactic multiple arc radiation therapy (SMART)] for pituitary adenomas not cured by conventional therapy. All 21 patients had undergone conventional radiotherapy (45-50 Gy); 18 had also undergone prior surgery. This cohort comprised 13 patients with somatotrope adenomas, four with corticotrope adenomas, one with a lactotrope adenoma, and three with nonfunctioning pituitary adenomas (median follow-up: 33 months, range: 3-72 months). SMART has proven effective, safe, and rapidly acting. We observed an accelerated reduction in GH and IGF-I levels in acromegaly, with normalization of GH and IGF-I levels in 58%. Mean GH fell from 21.1 mU/liter to 7.9 mU/liter (7 ng/ml to 2.6 ng/ml, P < 0.01, median 25 months) faster than our predicted fall to 50% at 2 yr with conventional radiotherapy. Mean IGF-I fell from 624 ng/ml to 384 ng/ml (P < 0.001). Tumor growth was controlled in two of three nonfunctioning pituitary adenomas, and three of four corticotrope adenomas. There were no adverse effects from SMART. Notably there have been no visual sequelae or further loss of anterior pituitary function in this heavily pretreated group. Our data indicate that SMART is an effective complementary therapy for pituitary adenomas that have displayed a suboptimal response to conventional therapy including external irradiation.

No abstract

123I is highly sensitive in diagnosing local recurrence and metastatic disease, and produces scintigraphic images which concord well with uptake following 131I therapy. It is proposed that 123I imaging, in combination with serum Tg measurements, should replace 131I tracer imaging as an indicator of the potential efficacy of 131I therapy. Stunning, with its detrimental effects on 131I therapy, may thus be avoided. The possibility of false negative images due to the stunning phenomenon must always be borne in mind if there is a discrepancy between positive 131I imaging studies and a surprisingly negative subsequent 131I therapy scan.

No abstract