Allen M. Chen

Evaluating the Role of Prophylactic Gastrostomy Tube Placement Prior to Definitive Chemoradiotherapy for Head and Neck Cancer

PURPOSE To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. METHODS AND MATERIALS One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. RESULTS Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). CONCLUSIONS Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.

Tobacco Smoking During Radiation Therapy for Head-and-Neck Cancer Is Associated With Unfavorable Outcome

PURPOSE To evaluate the effect of continued cigarette smoking among patients undergoing radiation therapy for head-and-neck cancer by comparing the clinical outcomes among active smokers and quitters. METHODS AND MATERIALS A review of medical records identified 101 patients with newly diagnosed squamous cell carcinoma of the head and neck who continued to smoke during radiation therapy. Each active smoker was matched to a control patient who had quit smoking before initiation of radiation therapy. Matching was based on tobacco history (pack-years), primary site, age, sex, Karnofsky Performance Status, disease stage, radiation dose, chemotherapy use, year of treatment, and whether surgical resection was performed. Outcomes were compared by use of Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer toxicity criteria. RESULTS With a median follow-up of 49 months, active smokers had significantly inferior 5-year overall survival (23% vs. 55%), locoregional control (58% vs. 69%), and disease-free survival (42% vs. 65%) compared with the former smokers who had quit before radiation therapy (p < 0.05 for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of Grade 3 or greater late complications was also significantly increased among active smokers compared with former smokers (49% vs. 31%, p = 0.01). CONCLUSIONS Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcomes. Further studies analyzing the biologic and molecular reasons underlying these differences are planned.

Prospective Study of Psychosocial Distress Among Patients Undergoing Radiotherapy for Head and Neck Cancer

PURPOSE To determine the prevalence of psychosocial distress among patients undergoing radiotherapy (RT) for head and neck cancer and to examine the association between depression and anxiety and demographic and medical variables. METHODS AND MATERIALS A total of 40 patients (25 men and 15 women) with nonmetastatic head and neck cancer were enrolled in this prospective study and underwent RT administered with definitive (24 patients) or postoperative (16 patients) intent. Twenty patients (50%) received concurrent chemotherapy. All patients completed the Hospital Anxiety and Depression Scale and Beck Depression Inventory-II instrument before RT, on the last day of RT, and at the first follow-up visit. The effect of patient-, tumor-, and treatment-related factors on psychosocial distress was analyzed. RESULTS The prevalence of mild to severe pre-RT depression was 58% and 45% using the Hospital Anxiety and Depression Scale-D and Beck Depression Inventory-II scale, respectively. The prevalence of severe pre-RT anxiety was 7%. The depression levels, as determined by the Hospital Anxiety and Depression Scale and Beck Depression Inventory-II instrument increased significantly during RT and remained elevated at the first follow-up visit (p < 0.001 for both). The variables that were significantly associated with post-RT depression included a greater pre-RT depression level, employment status (working at enrollment), younger age (<55 years), single marital status, and living alone (p < 0.05, for all). CONCLUSION The results of our study have shown that an alarming number of patients undergoing RT for head and neck cancer have symptoms suggestive of psychosocial distress even before beginning treatment. This proportion increases significantly during RT. Studies investigating the role of antidepressants and/or psychiatric counseling might be warranted in the future.

DEVELOPMENT AND VALIDATION OF A STANDARDIZED METHOD FOR CONTOURING THE BRACHIAL PLEXUS: PRELIMINARY DOSIMETRIC ANALYSIS AMONG PATIENTS TREATED WITH IMRT FOR HEAD-AND-NECK CANCER

PURPOSE Although Radiation Therapy Oncology Group protocols have proposed a limiting dose to the brachial plexus for patients undergoing intensity-modulated radiotherapy for head-and-neck cancer, essentially no recommendations exist for the delineation of this structure for treatment planning. METHODS AND MATERIALS Using anatomic texts, radiologic data, and magnetic resonance imaging, a standardized method for delineating the brachial plexus on 3-mm axial computed tomography images was devised. A neuroradiologist assisted with identification of the brachial plexus and adjacent structures. This organ at risk was then contoured on 10 consecutive patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. Dose-volume histogram curves were generated by applying the proposed brachial plexus contour to the initial treatment plan. RESULTS The total dose to the planning target volume ranged from 60 to 70 Gy (median, 70). The mean brachial plexus volume was 33 +/- 4 cm(3) (range, 25.1-39.4). The mean irradiated volumes of the brachial plexus were 50 Gy (17 +/- 3 cm(3)), 60 Gy (6 +/- 3 cm(3)), 66 Gy (2 +/- 1 cm(3)), 70 Gy (0 +/- 1 cm(3)). The maximal dose to the brachial plexus was 69.9 Gy (range, 62.3-76.9) and was >/=60 Gy, >/=66 Gy, and >/=70 Gy in 100%, 70%, and 30% of patients, respectively. CONCLUSIONS This technique provides a precise and accurate method for delineating the brachial plexus organ at risk on treatment planning computed tomography scans. Our dosimetric analysis suggest that for patients undergoing intensity-modulated radiotherapy for head-and-neck cancer, brachial plexus routinely receives doses in excess of historic and Radiation Therapy Oncology Group limits.

Down-regulation of microRNA 106b is involved in p21-mediated cell cycle arrest in response to radiation in prostate cancer cells.

microRNAs (miRNAs) are endogenous short non‐coding RNAs, and play a pivotal role in regulating of a variety of cellular processes, including proliferation and apoptosis, both of which are cellular responses to radiation treatment. The purpose of this study is to identify candidate miRNAs whose levels are altered in response to radiation in prostate cancer cells and to investigate the molecular pathway of such miRNAs in the regulation of radiation‐induced cellular response.

Clinical-dosimetric analysis of measures of dysphagia including gastrostomy-tube dependence among head and neck cancer patients treated definitively by intensity-modulated radiotherapy with concurrent chemotherapy

PurposeTo investigate the association between dose to various anatomical structures and dysphagia among patients with head and neck cancer treated by definitive intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy.Methods and materialsThirty-nine patients with squamous cancer of the head and neck were treated by definitive concurrent chemotherapy and IMRT to a median dose of 70 Gy (range, 68 to 72). In each patient, a gastrostomy tube (GT) was prophylacticly placed prior to starting treatment. Prolonged GT dependence was defined as exceeding the median GT duration of 192 days. Dysphagia was scored using standardized quality-of-life instruments. Dose-volume histogram (DVH) data incorporating the superior/middle pharyngeal constrictors (SMPC), inferior pharyngeal constrictor (IPC), cricoid pharyngeal inlet (CPI), and cervical esophagus (CE) were analyzed in relation to prolonged GT dependence, dysphagia, and weight loss.ResultsAt 3 months and 6 months after treatment, 87% and 44% of patients, respectively, were GT dependent. Spearmans ρ analysis identified statistical correlations (p < 0.05) between prolonged GT dependence or high grade dysphagia with IPC V65, IPC V60, IPC Dmean, and CPI Dmax. Logistic regression model showed that IPC V65 > 30%, IPC V60 > 60%, IPC Dmean > 60 Gy, and CPI Dmax > 62 Gy predicted for greater than 50% probability of prolonged GT dependence.ConclusionOur analysis suggests that adhering to the following parameters may decrease the risk of prolonged GT dependence and dysphagia: IPC V65 < 15%, IPC V60 < 40%, IPC Dmean < 55 Gy, and CPI Dmax < 60 Gy.

Comparison of peripheral dose from image-guided radiation therapy (IGRT) using kV cone beam CT to intensity-modulated radiation therapy (IMRT)

PURPOSE The growing use of IMRT with volumetric kilovoltage cone-beam computed tomography (kV-CBCT) for IGRT has increased concerns over the additional (typically unaccounted) radiation dose associated with the procedures. Published data quantify the in-field dose of IGRT and the peripheral dose from IMRT. This study adds to the data on dose outside the target area by measuring peripheral CBCT dose and comparing it with out-of-field IMRT dose. MATERIALS AND METHODS Measurements of the CBCT peripheral dose were made in an anthropomorphic phantom with TLDs and were compared to peripheral dose measurements for prostate IMRT, determined with MOSFET detectors. RESULTS Doses above 1cGy (per scan) were found outside the CBCT imaged volume, with 0.2cGy at 25 cm from the central axis. IMRT peripheral dose was 1cGy at 20 cm and 0.4cGy at 25 cm (per fraction). CONCLUSIONS An appreciable dose can be found beyond the edge of the IGRT field; of similar order of magnitude as peripheral dose from IMRT (mGy), and approximately half the dose delivered to the same point from the IMRT treatment (0.2cGy c.f. 0.4cGy 25 cm from the isocenter). This shows that peripheral dose, as well as the in-field dose from CBCT, needs to be taken into account when considering long term care of radiation oncology patients.

Practical Considerations in the Re-Irradiation of Recurrent and Second Primary Head-and-Neck Cancer: Who, Why, How, and How Much?

Despite progress in surgical and reconstructive techniques, as well as advances in radiotherapy delivery methods, a significant proportion of patients irradiated for head-and-neck cancer develop locoregional recurrence. These patients are also at high risk of developing new second primary cancers of the head and neck. Because of the heterogeneity of this population with respect to disease-related and patient-related factors, such as previous treatment, tumor recurrence site, disease extent, and performance status, the optimal treatment of locoregionally recurrent or second primary cancers of the head and neck remains to be defined. Although surgical resection typically constitutes the mainstay of treatment, effective salvage therapy is often precluded by anatomic inaccessibility and the risk of perioperative complications. Although chemotherapy alone has traditionally been considered an alternative to surgery, the response rates have been poor, with nearly all patients dying of disease progression within months. Similarly, salvage therapy using re-irradiation has historically been avoided because of concerns regarding toxicity. Although the results of more recent studies using contemporary treatment techniques and conformal delivery methods have been somewhat more promising, the role of re-irradiation after previous full-course radiotherapy is still considered investigational by many. Numerous questions remain unanswered, and practical guidelines for clinical decision-making are sparse.

Evaluation of the Planning Target Volume in the Treatment of Head and Neck Cancer With Intensity-Modulated Radiotherapy: What Is the Appropriate Expansion Margin in the Setting of Daily Image Guidance?

PURPOSE To compare patterns of disease failure among patients treated with intensity-modulated radiotherapy (IMRT) in conjunction with daily image-guided radiotherapy (IGRT) for head and neck cancer, according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV). METHODS AND MATERIALS Two-hundred and twenty-five patients were treated with IMRT for squamous cell carcinoma of the head and neck. Daily IGRT scans were acquired using either kilovoltage or megavoltage volumetric imaging prior to each delivered fraction. The first 95 patients were treated with IMRT with 5-mm CTV-to-PTV margins. The subsequent 130 patients were treated using 3-mm PTV expansion margins. RESULTS Two-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 76%, 78%, and 81%, respectively. There were no differences with respect to any of these endpoints among patients treated with 5-mm and 3-mm PTV expansion margins (p > 0.05, all). The 2-year local-regional control rate for patients treated with IMRT with 5-mm and 3-mm PTV margins was 78% and 78%, respectively (p = 0.96). Spatial evaluation revealed no differences in the incidences of marginal failures among those treated with 5-mm and 3-mm PTV margins. CONCLUSIONS The use of 3-mm PTV expansion margins appears adequate and did not increase local-regional failures among patients treated with IMRT for head and neck cancer. These data demonstrate the safety of PTV reduction of less than 5 mm and support current protocols recommending this approach in the setting of daily IGRT.

Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

PURPOSE To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. METHODS AND MATERIALS The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. RESULTS The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). CONCLUSIONS Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.