High-dose Clinical Target Volume Research Articles

Target Volume Definition for Intensity-modulated Radiotherapy after Induction Chemotherapy and Patterns of Treatment Failure after Sequential Chemoradiotherapy in Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma

AimsTo validate our approach to target volume definition for intensity-modulated radiotherapy (IMRT) after induction chemotherapy and to analyse the pattern of treatment failure in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (SCC) after sequential chemoradiotherapy (SCRT). Materials and methodsWe studied all patients with locoregionally advanced oropharyngeal SCC treated with SCRT, definitive IMRT and no prior surgery between December 2004 and February 2010. SCRT consisted of three cycles of induction chemotherapy followed by IMRT with concurrent weekly chemotherapy. Our approach to IMRT tumour volume definition after induction chemotherapy was similar to recommendations from published clinical practice guidelines. Volumetric expansion was used to create the high-dose clinical target volume with a margin of 10 mm. The high-dose planning target volume (PTV) was treated to 65 Gy, whereas the prophylactic-dose PTV received 54 Gy over 30 fractions using the simultaneous integrated boost technique. The location and extent of each treatment failure was recorded, reconstructed on the planning computed tomography images and analysed using the dose distribution of the IMRT plan. ResultsFifty-two patients were included. The median follow-up was 32.2 months (range 5.0–67.1 months). There were seven local failures, no regional recurrences and one with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. Actuarial recurrence-free, disease-specific and overall survival rates at 3 years were 83.9, 85.9 and 79.7%, respectively. ConclusionsThe absence of marginal recurrences validated the approach to IMRT target volume definition after induction chemotherapy proposed by clinical practice guidelines and practised at our institution. It suggested a lack of benefit with the use of larger geometric margins and additional anatomical expansion for the high-dose clinical target volume. SCRT resulted in excellent regional and distant disease control in patients with locoregionally advanced oropharyngeal SCC.

Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer

PurposeTo determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer. Materials and methodsAdaptive intensity-modulated radiotherapy was based on voxel intensity of pre-treatment and per-treatment [18F]fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG-PET) scans. Dose was escalated to a median total dose of 80.9Gy in the high-dose clinical target volume (dose level I) and 85.9Gy in the gross tumor volume (dose level II). The MTD would be reached, if ⩾33% of patients developed any grade ⩾4 toxicity (DLT) up to 3months follow-up. ResultsBetween February 2007 and August 2009, seven patients at dose level I and 14 at dose level II were treated. All patients completed treatment without interruption. At a median follow-up for surviving patients of 38 (dose level I) and 22months (dose level II) there was no grade ⩾4 toxicity during treatment and follow-up but six cases of mucosal ulcers at latency of 4–10months, of which five (36%) were observed at dose level II. Mucosal ulcers healed spontaneously in four patients. ConclusionsConsidering late mucosal ulcers as DLT, the MTD of a median dose of 80.9Gy has been reached in our trial.

Dose–volume analysis of locoregional recurrences in head and neck IMRT, as determined by deformable registration: A prospective multi-institutional trial

Background and purpose Although IMRT for head and neck cancer is widely accepted, the implications of sparing normal tissue immediately adjacent to target volumes are not well known. Materials and methods Between 2002 and 2007, 124 patients with head and neck cancer were treated with surgery and postoperative IMRT ( n = 79) or definitive RT ( n = 45). Locoregional recurrences were analyzed for location relative to target volumes, and dosimetry. Results With a median follow-up of 26.1 months, a total of 16 locoregional recurrences were observed. The five-year actuarial locoregional disease-free survival was 82% [95% CI, 72–90%]. Analysis of 18 distinct sites of locoregional failure revealed that five of these failures were within the high dose clinical target volume (CTV), nine failures were at the margin of the CTV, and four recurrences were outside the CTV. The mean dose delivered to these recurrent volumes was 63.1 Gy [range: 57–68 Gy], while the mean dose to the coolest 1 cc within each recurrence was 60.0 Gy [range: 51–67 Gy]. There were two periparotid recurrences observed. Conclusions We observed excellent locoregional control rates overall. The majority of recurrences occur within high dose regions of the neck and not near the spared parotid glands.

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography [(18)F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment (18)F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a (18)F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gy to the high-dose clinical target volume (CTV(high_dose)) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second (18)F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV(high_dose) (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV(high_dose) and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.

Target Volume Definition in Head and Neck IMRT Treatment Planning: Can We Omit High Dose Clinical Target Volume (CTV HD)?

Results: The 3-year overall survival rate was 70%. The cause-specific survival rates at 3 years were as follows: Stage I–II, 96%; Stage III, 75%; Stage IVA, 69%; and Stage IVB, 53%. All of loco-regional recurrences occurred within 2 years after radiotherapy. Twelve patients (2 with T1 disease and 10 with T2 disease) developed local recurrence and 6 of them were successfully salvaged with surgery. The 3-year local control rates for T1 and T2 disease were 89% and 83%, respectively. Nodal recurrence was observed in 16 patients. Among patients with N2b–N3 disease, the 3-year regional control rates were 87% for patients with neck dissection and 43% for patients without neck dissection. Conclusions: Patients with T1–2 hypopharyngeal cancer achieved a high chance of local control after definitive radiotherapy. For patients with advanced nodal disease, pre-radiotherapy planned neck dissection is an effective treatment resulting in high regional control. Author Disclosure: A. Nakajima, None; S. Nakamura, None; O. Suzuki, None; M. Morimoto, None; K. Nishiyama, None.

Margin on Gross Tumor Volume and Risk of Local Recurrence in Head-and-Neck Cancer

To determine whether the method or extent of construction of the high-dose clinical target volume (CTV) and high-dose planning target volume (PTV) in intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are associated with an increased risk of locoregional failure. Patients with nasopharyngeal, oropharyngeal, oral cavity, hypopharyngeal, or laryngeal squamous cell carcinomas treated definitively with IMRT were included. All patients without local relapse had a minimum follow-up of 12 months. Median follow-up for all patients was 24 months. Treatment plans of 85 available patients were reviewed, and the gross tumor volume (GTV) to PTV expansion method was estimated. The GTVs were expanded volumetrically in 71 of 85 patients, by a median of 15 mm (range, 4-25 mm). An anatomic component to the expansion of GTV was used in 14 of 85 patients. Eighteen patients failed locoregionally, for an actuarial locoregional control rate of 77.2% at 2 years. There was no significant difference in locoregional control between patients with GTVs expanded volumetrically vs. those with a component of anatomic expansion. In patients with GTVs expanded volumetrically, no increase in risk of local failure was seen in patients with a total GTV expansion of < or =15 mm. In this retrospective study, there was not an increased risk of local failure using smaller margins or expanding GTVs volumetrically when treating head-and-neck cancer patients definitively with IMRT.