D.L. Rash

Competing Causes of Death and Medical Comorbidities Among Patients With Human Papillomavirus-Positive vs Human Papillomavirus-Negative Oropharyngeal Carcinoma and Impact on Adherence to Radiotherapy

IMPORTANCE Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. OBJECTIVE To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. MAIN OUTCOMES AND MEASURES Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. RESULTS Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). CONCLUSIONS AND RELEVANCE Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

PURPOSE Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

Interfraction motion of the vaginal apex during postoperative intensity modulated radiation therapy: are we missing the target?

Objective This study aimed to evaluate changes in vaginal cuff position and rectal distention during whole pelvic intensity modulated radiation therapy using daily image guidance for patients with gynecologic malignancies. Materials and Methods We reviewed 145 daily images from 5 patients treated with intensity modulated radiation therapy after total abdominal hysterectomy for endometrial or cervical cancer. A fiducial marker was placed in the vaginal cuff tissue before computed tomographic simulation. The 2008 ASTRO consensus guidelines for delineation of clinical target volumes were used to deliver 45 to 50 Gy to the target structures. Daily megavoltage computed tomographic images were reviewed and changes in position of the fiducial marker as compared to the initial planning scan were recorded in the anterior-posterior (AP), lateral, and superior-inferior dimensions. Changes in rectal distention were also recorded. The position of the fiducial marker relative to the planning target volumes was reviewed on each daily image. Results The average shifts of the gold seed in the AP, lateral, and superior-inferior dimensions were 7 mm (range, 0–28 mm), 3 mm (range, 0–7 mm), and 2.9 mm (range, 0–12 mm), respectively. Distention of the rectum ranged from 20.5 to 60.1 mm and correlated with movement of the gold seed in the AP dimension (R = 0.53). For 2 patients, the fiducial marker was within 5 mm of the planning target volume margin on 8/40 treatments, or outside the planning target volume on 4/40 treatments. This did not significantly impact total delivered dose to the planning target volume. Conclusions Daily image guidance confirms significant interfraction movement of the vaginal cuff tissue, which may exceed suggested guidelines for clinical target volume margins.

The impact of a vaginal brachytherapy boost to pelvic radiation in stage III endometrial cancer

Purpose We investigate the use and impact of a vaginal brachytherapy boost (VBB) after pelvic radiotherapy for stage III endometrial adenocarcinoma on vaginal and pelvic control. Material and methods One hundred patients treated from 1998-2011 with surgery and adjuvant therapy with or without a VBB were included. Variables examined were grade, stage, lymphovascular space invasion (LVSI), vaginal involvement (VI), cervical stromal involvement (CSI), myometrial invasion (MI), and a VBB. Failure was scored as vaginal, or pelvic. Fishers exact test assessed association between variables with vaginal and pelvic control. Results With a median follow up of 43 months, 31% were stage IIIA, 6% stage IIIB, and 63% stage IIIC. Thirty-eight (38%) received pelvic radiotherapy alone, and 62% received adjuvant chemotherapy. Of the 100 patients, 82 were treated with a VBB, 10 were not treated with a VBB, and 8 were not treated with RT. Of the 82 patients who received a VBB, 5 failed in the vagina with vaginal and pelvic control rates of 94% and 92%. The impact of VB reached borderline significance with its impact on pelvic control, 92% vs. 70% (p = 0.056), and did not affect vaginal control, 94% and 90% (p = 0.50). Neither tumor grade, LVSI, CSI, stage, nor LVSI (p > 0.05) statistically significantly impacted vaginal control. Conclusions There are no clinical guidelines for the use of a VBB in stage III endometrial cancer. The majority of our patients were treated with a VBB and experienced excellent pelvic and vaginal control. The presence of traditional adverse features did not negatively impact control in our patient cohort. However, the role of a VBB needs further investigation to understand the incremental benefit beyond pelvic RT.

Dose delivered to the lumbosacral plexus from high-dose-rate brachytherapy for cervical cancer

Objective To calculate dose delivered to the lumbosacral plexus (LSP) with cervical brachytherapy using 3-dimensional imaging, and to compare this with the position of the tandem in the pelvis using bony landmarks. We also report long-term LSP toxicity outcomes. Methods and Materials Treatment planning images from 55 patients treated with tandem and ring brachytherapy from October 2009 through November 2012 were reviewed. The LSP was contoured on planning computed tomographic scans to calculate dose received. Lumbosacral plexus dose was studied as a function of tandem distance from the sacrum and pubic symphysis (STratio) measured on digitally reconstructed radiographs. Patient and implant characteristics were included as covariates on LSP dose. Clinical follow up on LSP toxicity was recorded. Results Patients were prescribed 550 to 700 cGy using computed tomography–based imaged-guided brachytherapy for 4 to 5 fractions. The maximum dose to 2 cc (D2cc) of LSP ranged from 44 to 287 cGy per implant. The median D2cc was 118 cGy, corresponding to 18% of prescription dose. Patients with an STratio less than 0.33 (closer to the sacrum) and at least 0.33 had median LSP doses of 138 and 98 cGy, respectively. Lumbosacral plexus dose did not change significantly with body mass index, uterus position, or tumor stage. Two patients reported symptoms of peripheral neuropathy, with a median follow-up of 14.7 months. Conclusions The mean D2cc per fraction to the LSP is roughly 20% of the prescribed high dose-rate and varies with the position of the tandem from the sacrum. The dose threshold for radiation-induced neuropathy of the LSP remains undefined.

Pelvic and Paraortic Lymph Node Response to Chemoradiation Therapy in Patients With Locally Advanced Cervical Cancer: Does a Higher Boost Dose Impact Nodal Control?

HR-CTV D90 -5.0 8 -3.0 6 -1.7 4 -0.9 2 0.4 2 1.0 5 1.2 8 1.4 13 HR-CTV D100 -6.2 11 -3.9 8 -2.4 5 -1.0 2 1.0 3 2.3 4 3.2 8 3.8 14 Rectum D2cc 37.1 5 22.5 3 12.9 2 6.3 1 -5.1 1 -9.8 2 -15.3 4 -21.4 6 Bladder D2cc -11.0 5 -7.5 3 -4.9 2 -2.6 1 2.5 1 5.4 2 9.6 4 15.4 6 Sigmoid D2cc -6.7 7 -4.1 5 -2.5 3 -1.2 1 0.7 1 1.5 2 2.4 4 3.2 6 Point A Left -5.5 9 -3.2 6 -1.8 4 -0.8 2 0.7 2 1.2 5 1.9 8 2.8 12 Point A Right -7.0 11 -4.5 8 -2.8 5 -1.5 3 1.1 3 2.7 6 4.7 11 7.5 19 ICRU Rectum 23.7 27 14.9 16 8.7 9 4.3 4 -4.1 3 -8.2 6 -13.5 9 -20.0 12 ICRU Bladder -4.2 10 -2.6 7 -1.6 5 -0.7 2 0.7 2 1.6 5 2.5 9 3.9 15 Volume 84 Number 3S Supplement 2012 Poster Viewing Abstracts S435