Aspiration pneumonia after chemo-intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors.

BACKGROUND: The purpose of this study was to assess aspiration pneumonia (AsPn) rates and predictors after chemo-irradiation for head and neck cancer. METHODS: The was a prospective study of 72 patients with stage III to IV oropharyngeal cancer treated definitively with intensity-modulated radiotherapy (IMRT) concurrent with weekly carboplatin and paclitaxel. AsPn was recorded prospectively and dysphagia was evaluated longitudinally through 2 years posttherapy by observer-rated (Common Toxicity Criteria version [CTCAE]) scores, patient-reported scores, and videofluoroscopy. RESULTS: Sixteen patients (20%) developed AsPn. Predictive factors included T classification (p = .01), aspiration detected on videofluoroscopy (videofluoroscopy-asp; p = .0007), and patient-reported dysphagia (p = .02-.0003), but not observer-rated dysphagia (p = .4). Combining T classification, patient reported dysphagia, and videofluoroscopy-asp, provided the best predictive model. CONCLUSION: AsPn continues to be an under-reported consequence of chemo-irradiation for head and neck cancer. These data support using patient-reported dysphagia to identify high-risk patients requiring videofluoroscopy evaluation for preventive measures. Reducing videofluoroscopy-asp rates, by reducing swallowing structures radiation doses and by trials reducing treatment intensity in patients predicted to do well, are likely to reduce AsPn rates.

Neck spasm after chemoradiotherapy for head and neck cancer: natural history and dosimetric correlates.

BACKGROUND: Little is known about the determinants of postradiation neck spasms in patients with head and neck cancer. METHODS: Patients with head and neck cancer treated with radiation therapy (RT) from 2004 to 2010 who experienced neck spasms werereviewed. Radiation doses were generated for their sternocleidomastoid (SCM) muscles bilaterally. Unaffected SCMs were used as controls. RESULTS: Thirty-four patients reported neck spasms. Thirty had received definitive chemoradiation, and 4 had RT alone. Seven also had an ipsilateral neck dissection. Median time to onset was 23 months (range, 6-67 months). There were significantly higher radiation doses to the affected SCMs with a median of the mean dose to the affected and unaffected SCM of 62.3 Gy (range, 29-71 Gy) and 53.7 Gy (range, 27-65 Gy), respectively (p < .0001). Other dosimetric variables were also statistically significant but were highly correlated with the mean SCM dose. Neck dissection did not affect our results. CONCLUSION: Neck spasms after chemotherapy intensity-modulated radiation therapy (IMRT) shows a strong dose-response relationship.

Parotid glands dose-effect relationships based on their actually delivered doses: implications for adaptive replanning in radiation therapy of head-and-neck cancer.

PURPOSE: Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses. METHODS AND MATERIALS: In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative delivered doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy. RESULTS: Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were -4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose-effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments. CONCLUSIONS: After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose-saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.

Clinical review of physical activity and functional considerations in head and neck cancer patients.

Patients facing head and neck cancer treatment are profoundly vulnerable to physiologic and functional disability. Exercise and nutrition have been shown to have many benefits in cancer patients, but much of this work has been performed in groups of breast, colon, and prostate cancer patients. Limited data exists regarding the role of exercise and nutrition in the management of head and neck cancer patients given their unique set of challenges relating to the cancer as well as its treatment. In this paper, we review the existing literature about general or recreational physical exercise as well as nutrition in this patient population as it pertains to lean muscle body composition, functional well-being, and overall quality of life.

Toxicities affecting quality of life after chemo-IMRT of oropharyngeal cancer: prospective study of patient-reported, observer-rated, and objective outcomes.

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) aiming to spare the salivary glands and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life (QOL). METHODS AND MATERIALS: In this prospective, longitudinal study, 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary glands and swallowing structures. Overall QOL was assessed by summary scores of the Head Neck QOL (HNQOL) and University of Washington QOL (UWQOL) questionnaires, as well as the HNQOL "Overall Bother" question. Quality of life, observer-rated toxicities (Common Toxicity Criteria Adverse Effects scale, version 2), and objective evaluations (videofluoroscopy assessing dysphagia and saliva flow rates assessing xerostomia) were recorded from before therapy through 2 years after therapy. Correlations between toxicities/objective evaluations and overall QOL were assessed using longitudinal repeated measures of analysis and Pearson correlations. RESULTS: All observer-rated toxicities and QOL scores worsened 1-3 months after therapy and improved through 12 months, with minor further improvements through 24 months. At 12 months, dysphagia grades 0-1, 2, and 3, were observed in 95%, 4%, and 1% of patients, respectively. Using all posttherapy observations, observer-rated dysphagia was highly correlated with all overall QOL measures (P<.0001), whereas xerostomia and mucosal and voice toxicities were significantly correlated with some, but not all, overall QOL measures, with lower correlation coefficients than dysphagia. Late overall QOL (≥6 or ≥12 months after therapy) was primarily associated with observer-rated dysphagia, and to a lesser extent with xerostomia. Videofluoroscopy scores, but not salivary flows, were significantly correlated with some of the overall QOL measures. CONCLUSION: After chemo-IMRT, although late dysphagia was on average mild, it was still the major correlate of QOL. Further efforts to reduce swallowing dysfunction are likely to yield additional gains in QOL.

Radiation therapy with full-dose gemcitabine and oxaliplatin for unresectable pancreatic cancer.

PURPOSE: We completed a Phase I trial of gemcitabine and oxaliplatin with concurrent radiotherapy in patients with previously untreated pancreatic cancer. The results of a subset of patients with unresectable disease who went on to receive planned additional therapy are reported here. METHODS AND MATERIALS: All patients received two 28-day cycles of gemcitabine (1,000 mg/m(2) on Days 1, 8, and 15) and oxaliplatin (40-85 mg/m(2) on Days 1 and 15, per a dose-escalation schema). Radiation therapy was delivered concurrently with Cycle 1 (27 Gy in 1.8-Gy fractions). At 9 weeks, patients were reassessed for resectability. Those deemed to have unresectable disease were offered a second round of treatment consisting of 2 cycles of gemcitabine and oxaliplatin and 27 Gy of radiation therapy (total, 54 Gy). Radiation was delivered to the gross tumor volume plus 1 cm by use of a three-dimensional conformal technique. We used the Common Terminology Criteria for Adverse Events to assess acute toxicity. Late toxicity was scored per the Radiation Therapy Oncology Group scale. Computed tomography scans were reviewed to determine pattern of failure, local response, and disease progression. Kaplan-Meier methodology and Cox regression models were used to evaluate survival and freedom from failure. RESULTS: Thirty-two patients from the Phase I dose-escalation study had unresectable disease, three of whom had low-volume metastatic disease. Of this group, 16 patients went on to receive additional therapy to complete a total of 4 cycles of chemotherapy and 54 Gy of concurrent radiation. For this subset, 38% had at least a partial tumor response at a median of 3.2 months. Median survival was 11.8 months (range, 4.4-26.3 months). The 1-year freedom from local progression rate was 93.8% (95% confidence interval, 63.2-99.1). CONCLUSIONS: Radiation therapy to 54 Gy with concurrent full-dose gemcitabine and oxaliplatin is well tolerated and results in favorable rates of local tumor response and 1-year freedom from local progression.

Pattern of failure after high-dose thoracic radiation for non-small cell lung cancer: the University of Michigan experience.

PURPOSE: Our main purpose is to study the pattern of local failure for patients with non-small cell lung cancer treated with conformal therapy. METHODS: This study included patients who failed locally and a matched group without failures after 3D conformal radiation per a radiation dose-escalation trial. Radiation doses ranged from 65.1 to 102.9 Gy in 2.1 Gy fractions, originally computed using an equivalent path length algorithm. The recurrent gross target volumes (RGTV) were contoured. The original and recurrent planning target volume (PTV and RPTV) were generated by 1 cm uniform expansion from GTV. DVHs and generalized equivalent uniform doses (EUD={Σ i (di ) a }1/a ) were computed. Marginal failures were defined for RGTVs covered by the original 10 to 90 % isodose surfaces. RESULTS: There were no significant differences between the failed and control groups with regard to average original GTV volumes, GTV and PTV doses, and minimum PTV doses. Of the 18 RGTVs, four had marginal failure, 12 failed mostly within, and two failed outside of the original PTV. The mean EUDs were 57.1 Gy (95 % confidence interval (CI) 43.9-70.6) and 47.5 Gy (95 % CI 33.7-61.2), for the RGTVs and RPTVs, respectively, significantly below the prescribed doses (p=0.03). EUDs were less than 60 Gy for 39 % of the RGTVs and 56 % of the RPTVs. CONCLUSIONS: Recurrent tumors had significantly lower doses than the prescribed dose suggesting that some of these failures could have been avoided with modern technology such as 4D CT simulation and image-guided radiation therapy.

Advances in imaging: target delineation.

Modern radiation oncology relies heavily on emerging technology. In this article, we review recent advances in target delineation as it applies to radiation treatment planning. We focus on the evidence to support methionine positron emission tomography use for target delineation in primary brain tumors, 2-deoxy-2-[(18)F] fluoro-D-glucose positron emission tomography use for target delineation for lung cancer and head and neck cancer, and the use of magnetic resonance imaging sequences for target delineation in prostate cancer.