Adaptive radiotherapy for head and neck cancers: Fact or fallacy to improve therapeutic ratio?

Modern standards of precision radiotherapy, primarily driven by the technological advances of intensity modulation and image guidance, have led to increased versatility in radiotherapy planning and delivery. The ability to shape doses around critical normal organs, while simultaneously "painting" boost doses to the tumor have translated to substantial therapeutic gains in head and neck cancer patients. Recently, dose adaptation (or adaptive radiotherapy) has been proposed as a novel concept to enhance the therapeutic ratio of head and neck radiotherapy, facilitated in part by the onset of molecular and functional imaging. These contemporary imaging techniques have enabled visualisation of the spatial molecular architecture of the tumor. Daily cone-beam imaging, besides improving treatment accuracy, offers another unique angle to explore radiomics - a novel high throughput feature extraction and selection workflow, for adapting radiotherapy based on real-time tumor changes. Here, we review the existing evidence of molecular and functional imaging in head and neck cancers, as well as the current application of adaptive radiotherapy in the treatment of this tumor type. We propose that adaptive radiotherapy can be further exploited through a systematic application of molecular and functional imaging, including radiomics, at the different phases of planning and treatment.

Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

BACKGROUND: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible. RESULTS: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively. CONCLUSIONS: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.