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A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

ABSTRACT: PURPOSE:To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ?G2 subjective xerostomia. METHODS:Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing IMRT. The primary site and involved nodal levels received 65?Gy in 30 fractions (f) and at risk nodal levels, 54?Gy/30f. Incidence of ?G2 subjective xerostomia was defined as the primary endpoint. Secondary endpoints included incidences of acute and late toxicities and survival outcomes dependent on human papilloma virus (HPV) status. RESULTS:One hundred and twenty patients with midline cancers completed treatment between December 2005 and May 2010 with median follow-up of 50 months. Incidences of ?G2 acute toxicities were: dysphagia 75%; xerostomia 65%; mucositis 86%; pain 83%; and fatigue 64%. At 12 months, ?G2 subjective xerostomia was observed in 21% (17% in HPV +ve). Two-year loco-regional progression-free survival (PFS) was 90.7% (95% CI: 85.2-96.2). According to HPV status, there was a significant difference for 2-year loco-regional PFS, 76.8% (HPV-negative) vs 98.6% (HPV-positive), P=0.001. 2-year overall survival was 93% for HPV-positive compared with 52% for HPV-negative cases, P<0.001. CONCLUSIONS:Sequential chemotherapy/chemo-IMRT for midline tumours is feasible, with excellent survival outcomes. At 1 year, 21% experience ?G2 subjective xerostomia. Two-year survival outcomes differ significantly between HPV-positive and HPV-negative disease, suggesting development of different treatment schedules for the different disease entities.

SUBMITTER: Miah AB

PROVIDER: S-EPMC4453605 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

Miah A B AB Schick U U Bhide S A SA Guerrero-Urbano M-T MT Clark C H CH Bidmead A M AM Bodla S S Del Rosario L L Thway K K Wilson P P Newbold K L KL Harrington K J KJ Nutting C M CM

British journal of cancer 20141204 1

<h4>Purpose</h4>To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia.<h4>Methods</h4>Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing ...[more]

PMID: 25474250

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Project description:To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands.In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors.Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points.The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone.

Project description:Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data.Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test.Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined model differ from actual values by only 2.2 Gy (p = 0.005). Similarly, the sum of residues between the modeled and the actual plan DVHs is the same for the bilateral sparing cases by both models (p = 0.67), while the standard model predicts significantly higher DVHs than the combined model for the single-side sparing cases (p = 0.01).The combined model for predicting parotid sparing that takes into account single-side sparing improves the prediction accuracy over the previous model.

Project description:PurposeRadical radiotherapy for head and neck cancer (HNC) may deliver significant doses to brain structures. There is evidence that this may cause a decline in neurocognitive function (NCF). Radiation dose to the medial temporal lobes, and particularly to the hippocampi, seems to be critical in determining NCF outcomes. We evaluated the feasibility of two alternative intensity-modulated radiotherapy (IMRT) techniques to generate hippocampus- and brain-sparing HNC treatment plans to preserve NCF.Methods and materialsA planning study was undertaken for ten patients with HNC whose planning target volume (PTV) included the nasopharynx. Patients had been previously treated using standard (chemo)-IMRT techniques. Bilateral hippocampi were delineated according to the RTOG atlas, on T1w MRI co-registered to the RT planning CT. Hippocampus-sparing plans (HSRT), and whole-brain/hippocampus-sparing fixed-field non-coplanar IMRT (BSRT) plans, were generated. DVHs and dose difference maps were used to compare plans. NTCP calculations for NCF impairment, based on hippocampal dosimetry, were performed for all plans.ResultsSignificant reductions in hippocampal doses relative to standard plans were achieved in eight of ten cases for both HSRT and BSRT. EQD2 D40% to bilateral hippocampi was significantly reduced from a mean of 23.5 Gy (range 14.5-35.0) in the standard plans to a mean of 8.6 Gy (4.2-24.7) for HSRT (p = 0.001) and a mean of 9.0 Gy (4.3-17.3) for BSRT (p < 0.001). Both HSRT and BSRT resulted in a significant reduction in doses to the whole brain, brain stem, and cerebellum.ConclusionWe demonstrate that IMRT plans for HNC involving the nasopharynx can be successfully optimised to significantly reduce dose to the bilateral hippocampi and whole brain. The magnitude of the achievable dose reductions results in significant reductions in the probability of radiation-induced NCF decline. These results could readily be translated into a future clinical trial.

Project description:This clinical study was designed to prospectively evaluate the acute and moderately-late cardiac and lung toxicities of intensity modulated radiation therapy delivered by helical tomotherapy (IMRT-HT) for locoregional breast radiation treatment including the internal mammary nodes (IMN).30 patients with stage III breast cancers have been accrued in this study. All patients received adjuvant chemotherapy. Target volumes were defined as follows: the PTV included breast/chest wall, axillary level II, III, infra/supraclavicular, IM nodes CTVs plus 3 mm margins. The heart with subunits and the lungs were defined as critical organs. Dose to PTV was 50 Gy in 25 fractions. Acute toxicities were assessed every week and 2 weeks post treatment using the CTCAE v3.0.scale. The moderately-late toxicities were assessed clinically plus by cardiac myoview perfusion tests scheduled at baseline, 3 and 12-month follow-up, as well a CT chest at the 6 month follow-up. The data analysis is descriptive.All participants completed the 5-week course of radiation without interruption. Skin erythema was modest and mainly grade 1-2 between the 3rd and the 5th week of radiation treatment. Only 4/30 patients experienced grade 3 skin reactions, mostly seen 2 weeks post radiation. Only 5 patients demonstrated grade 1 or 2 dyspnea, but 3 of them already had symptoms pre-radiation treatment. With a median follow-up of 58 (24-76) months, there have been infrequent moderately-late side effects. Most were grade 1 and were sometimes present at the baseline assessment. Cardiac myoview tests done at baseline and 1-year follow-up for 15 out of 18 left sided breast cancers did not show any abnormalities related to radiation. The 6-month follow-up chest CT-scans done for 25 out of 30 patients showed minimal anterior lung fibrosis for 7 patients and were completely normal for the other 18. No locoregional recurrence has been recorded and the 5-year survival is 78% (95% CI: 70-97%).IMRT-HT for locoregional breast radiation is very well tolerated with minimal acute or moderately-late side effects. Cardiac and respiratory tests did not show any strong evidence of significant treatment related abnormalities.clinicaltrials.gov: http://NCT00508352.

Project description:Not all clinics have breath-hold radiotherapy available for left-breast irradiation. However intensity-modulated radiotherapy (IMRT) has also been advocated as a means of lowering heart doses. There is currently no large-scale, long-term follow-up data after breast IMRT and, since dose distributions may differ from classic tangent-based radiotherapy, caution is needed to avoid unexpected worsening of the late toxicity profile. We compared four IMRT techniques for free-breathing left-breast irradiation. Consistent with the aforementioned concerns, our goal in planning was to prioritize organ at risk (OAR) sparing in a way that mimicked tangent-based radiotherapy. Ten simultaneous integrated boost treatment plans (PTVelective = 15 × 2.67 Gy; PTVboost = 15 × 3.35 Gy) were created using 1) hybrid-IMRT (H-IMRT), 2) full IMRT (F-IMRT), and 3) volumetric-modulated arc therapy with two partial arcs (2ARC) and 4) six partial arcs (6ARC). Reduction in OAR mean and low dose was prioritized. End-points included OAR sparing (e.g., heart, left anterior descending artery [LAD+3 mm], lungs, and contralateral breast) and PTV coverage/dose homogeneity. Under these conditions we found the following: 1) H-IMRT provided the best mean and low dose OAR sparing, PTVelective coverage (mean V95% = 98%), PTVboost coverage (V95% = 98%), and PTV homogeneity. However, it delivered most intermediate-high dose to the heart, LAD+3 mm and ipsilateral lung; 2) 6ARC had the best intermediate-high dose sparing, followed by F-IMRT, but this was at the expense of more dose in the contralateral lung and breast and worse PTV coverage (PTVelective mean V95% = 96%/97% and PTVboost mean V95% = 91%/96% for 6ARC/F-IMRT). When trying to spare mean and low dose to OARs, the preferred IMRT technique for left-breast irradiation without breath-hold was H-IMRT. This is currently the standard solution in our institution for left-breast radiotherapy under free-breathing and breath-hold conditions.

Dataset Information

A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

Publications

A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

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