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This study compare dosimetric parameters and secondary malignancy risk (SMN) using intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans for the treatment of sinonasal cancer (SC). After IRB-approval, 10 patients previously treated with IMPT for cancers of the ethmoid, sphenoid, maxillary, or frontal sinuses were identified. Dosimetrists blinded to the IMPT plans generated VMAT plans for comparison. Volume coverage and dose to organs at risk (OAR) were recorded and compared. Organ equivalent dose (OED) of tissues outside of the treatment volume was used to define the excess absolute and relative risk of SMNs. In all cases, both VMAT and IMPT provided acceptable target volume coverage and were able to meet OAR constraints. IMPT was superior for brain V10, V30, and mean, brainstem D0.01 ipsilateral cochlea V30, contralateral cochlea mean, contralateral lacrimal gland mean, contralateral parotid mean, spinal cord D0.01 and body outside of the CTV V10, V20, and V30. VMAT was superior for ipsilateral eye mean, ipsilateral lens mean, CTV V100 and maximum hotspot. The relative risk of SMNs with VMAT compared to IMPT is 3.35 (95% CI, 1.92-5.89). For the treatment of SC, IMPT spares OARs that are not immediately adjacent to the treatment volume and reduces the risk of SMNs when compared to VMAT. VMAT spares OARs abutting the target volume better than IMPT and has more homogenous target coverage. Tumors of the ethmoid sinus, benefit more from IMPT, while tumors located elsewhere require application of our findings on a case by case basis.

Introduction Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Material and methods Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Results Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. Conclusion International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

Osteoradionecrosis is a relatively rare but potentially morbid and costly complication of radiation therapy for head and neck cancer. Multidisciplinary diagnosis and treatment are essential. Despite evidence guiding individual aspects of care for osteoradionecrosis, there is a lack of broad consensus on the overall diagnosis and management of this condition. This study comprehensively reviews the literature, with a focus on the past 10 years, to guide evaluation and treatment.

OBJECTIVES: Salvage surgical resection is the preferred treatment for head and neck squamous cell carcinoma (HNSCC) patients who develop locally recurrent disease after failing primary therapy. However, salvage surgical resection is not always feasible, and survival outcomes for those that do undergo salvage remain poor. It is well known that patients with adverse pathological features (extracapsular extension (ECE) of lymph nodes (LN), positive margins, peri-neural spread (PNI), lymphovascular invasion (LVI), and multiple LN metastases) at the time of primary surgical resection are likely to have relatively poor outcomes. However, the impact of adverse pathological features on outcomes in the salvage setting remains controversial. MATERIALS AND METHODS: We retrospectively analyzed 73 patients at a single institution from 2008–2017 who developed recurrence and subsequently underwent salvage surgery (SS) after definitive curative-intent therapy including radiation. Demographic and disease control outcomes were reviewed. Kaplan-Meier curves were used to estimate relapse free survival (RFS) and overall survival (OS). RESULTS: Median age at diagnosis was 61 years (range 40–86), 49/73 (67%) were male, and 55/73 (75%) had smoked. Patients with any adverse pathological features at SS had worse RFS (HR 3.15 p=0.0008) and worse OS (3.97 p=0.0008). Patients who relapsed

PURPOSE/OBJECTIVE(S) Given the historical toxicity of radiotherapy for head & neck cancer, there has been an emphasis on de-escalation for patients with favorable disease features. The use of unilateral radiation to cervical nodes is a prominent de-escalation strategy in well-lateralized tonsil cancers. However, the safety of this approach for patients with AJCC-7 N2b disease was less well-established in the landmark studies guiding its use. The study hypothesis was that unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer results in a low rate of contralateral nodal failure. MATERIALS/METHODS This study was a retrospective chart review of 66 patients treated from 2005 to 2016 at two academic institutions. Eligible patients had AJCC-7 T1-2N2b squamous cell carcinoma of the tonsil and were treated with unilateral radiation therapy. The primary endpoint was the rate of contralateral nodal failure at the time of last follow-up. Ipsilateral recurrence rates and overall survival were additional endpoints of interest. When available, data were collected regarding the presence of clinical extracapsular extension (ECE). Human papillomavirus/p16 status was also assessed. RESULTS The median age at diagnosis was 55.5 years and 53 patients (80.3%) were male. 38 patients (57.6%) had T1 disease and 28 patients (42.4%) had T2 disease based upon AJCC-7 staging. Of the 52 patients who had information on tumor HPV status, all were positive. In regards to systemic therapy, 18 patients (27.3%) had induction therapy, 26 (39.4%) had concurrent therapy, and 4 (6.1%) had both. The median time to last post-radiation follow-up was 80.9 months; 87.9% of patients remained alive at last follow-up and median OS was not reached. Contralateral nodal failure occurred in 2/66 (3.0%) patients at 3.6 and 20.9 months, respectively. Both patients underwent salvage treatment. The first survived an additional 65 months and the second remains alive at last follow-up 37 months after recurrence. Sixteen patients (24.2%) were felt to have extracapsular extension by clinical exam, radiology, or pathology; one of the two contralateral recurrences occurred in this group. Two patients (3%) experienced recurrence at the treated primary site and/or neck. Overall locoregional control at both 2 and 5 years was 93.9% and the median duration of control was not reached. CONCLUSION The use of unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer resulted in low rates of contralateral nodal failure. This outcome demonstrates the safety of considering unilateral treatment in patients with a high ipsilateral nodal burden. Further assessments are needed to determine the impact of radiation volume reduction on patient quality of life.

Purpose/Objective(s) Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal squamous cell carcinoma, but long-term survival remains suboptimal, warranting an improved approach. Immunotherapy has been studied in the metastatic and unresectable recurrent setting, but additional data are needed to assess its role in definitive therapy. The study hypothesis was that the use of immunotherapy in conjunction with chemoradiation would be safe and result in improved laryngectomy-free survival (LFS) compared to standard of care chemoradiation. Materials/Methods This trial was an open-label, single-arm, prospective, multi-institutional study. The study included a Phase I run-in portion to assess safety in the first 6 enrolled patients and a planned subsequent Phase II component. Due to slow accrual, the study was closed after enrollment of 9 patients and the data were allowed to mature. The primary endpoint of the Phase II portion was LFS at 18 months. Study patients had Stage III or IV (T1-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given as a 200 mg flat dose 3 weeks prior to the start of chemoradiation and was then given q21 days until the completion of chemoradiation. Cisplatin was given at a dose of 100 mg/m2 q21 days during radiation with allowed dose modifications for toxicities. Radiation was prescribed to a total dose of 70 Gy in 35 daily fractions using IMRT with an elective nodal dose of 56-63 Gy. Results A total of 9 patients with a median age of 54 were enrolled from 2017 to 2019. The median follow-up time was 30.1 months. None of the enrolled patients required laryngectomy, resulting in 100% LFS at 18 months for evaluable patients. The 18-month overall survival (OS) rate was 66.7%; of the 3 patient deaths, 2 were due to co-morbid conditions (diabetes, peripheral arterial disease) rather than malignancy. The remaining 6 patients were alive at the time of last follow-up and the median duration of OS was not reached. There were 27 Grade 3 toxicities, with 2 attributable to pembrolizumab. Nearly all Grade 4 (n = 4) and Grade 5 (n = 1) toxicities occurred in a single patient with poorly-controlled diabetes; the Grade 5 toxicity was due to diabetic ketoacidosis. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation; the edema has since resolved and the tracheostomy was reversed. Conclusion The use of concurrent pembrolizumab with chemoradiation for locally advanced larynx cancer resulted in high LFS. Most toxicities were attributable to chemoradiation and the majority of Grade 4 and 5 toxicities occurred in a patient with poorly-controlled diabetes. A case of late Grade 4 laryngeal edema could have been related to immunotherapy. Future studies with concurrent immunotherapy with chemoradiation should account for this possibility.

Background The prognostic value of pretreatment complete blood count (CBC) data, including absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), has been reported for many diseases with decreased ALC and increased absolute neutrophil count (ANC) and NLR values correlating with worse outcomes. There is minimal data relating these hematologic parameters to oropharyngeal squamous cell carcinoma (OPSCC) prognosis. This study evaluates the prognostic value of pretreatment CBC data in OPSCC on overall survival (OS) and progression-free survival (PFS) in relation to HPV status. Methods A single-institutional retrospective review of patients with pretreatment hematologic data who received radiation for OPSCC was performed. Univariate and multivariate (UVA/MVA) Cox proportional hazard regression analyses were performed to identify prognostic variables. Translational studies related outcomes to the degree of tumor-infiltrating lymphocytes (TILs) in histologic specimens. Results From 2007 to 2018, 201 patients were treated for OPSCC. Median follow-up was 40 months. 3-year OS was 86.2% in the HPV-positive cohort, 46.3% for HPV-negative. Median NLR was 3.04. NLR ≥ 3 was associated with worse PFS (HR 1.67, p = 0.044. In the subset of 158 HPV + patients, MVA revealed increasing ALC to be associated with improved OS (HR 0.53; p = 0.040) and PFS (HR = 0.48; p = 0.0075). On UVA, high-TIL infiltration at diagnosis was associated with improved OS. Conclusion In a cohort of HPV + OPSCC patients, increasing ALC is associated with improved OS and PFS. Our study is the first to identify pre-treatment ALC as an independent prognostic factor in HPV-associated OPSCC.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and often fatal disease. Cisplatin is the most common chemotherapeutic drug in the treatment of HNSCC, but intrinsic and acquired resistance are frequent, and severe side effects occur at high doses. The second messenger cyclic GMP (cGMP) is produced by soluble guanylate cyclase (sGC). We previously reported that activation of the cGMP signaling cascade caused apoptosis in HNSCC cells, while others found that this pathway enhances cisplatin efficacy in some cell types. Here we found that sGC stimulators reduced HNSCC cell viability synergistically with cisplatin, and enhanced apoptosis by cisplatin. Moreover, the sGC stimulators effectively reduced viability in cells with acquired cisplatin resistance, and were synergistic with cisplatin. The sGC stimulator BAY 41-2272 reduced expression of the survival proteins EGFR and β-catenin, and increased pro-apoptotic Bax, suggesting a potential mechanism for the anti-tumorigenic effects of these drugs. The sGC stimulator Riociguat is FDA-approved to treat pulmonary hypertension, and others are being studied for therapeutic use in several diseases. These drugs could provide valuable addition or alternative to cisplatin in the treatment of HNSCC.

OBJECTIVES: Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). MATERIALS AND METHODS: Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas’s transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. RESULTS: APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p=0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p

Purpose Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. Methods and Materials We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. Results The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure–free survival, overall survival, progression-free survival, and distant metastasis–free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Conclusions Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.

This case series describes the use of pelvic radiotherapy (RT) and MRI-based intracavitary brachytherapy (ICBT) for patients with small volume, early-stage, primary vaginal cancer. A customized pelvic MRI protocol with a vaginal cylinder in place (MRVC) was used to measure disease extent and tumor thickness (defined as distance from lateral/apical margin of tumor to cylinder surface) at time of diagnosis. Non-bulky tumors with initial (pre-RT) thickness ≤ 2 cm from the cylinder surface received pelvic RT followed by ICBT. Ten patients with FIGO stage I–II primary vaginal cancer treated with pelvic RT +/− cisplatin and ICBT at our institution between 1998 and 2008 were included. Initial tumor thickness measured on MRVC ranged from 0 to 2 cm. Initial tumor volume ranged from 0 to 9.8 cm3. Mean pelvic RT dose was 45 Gy. At the time of ICBT, 60% of patients had a complete response (cR) and 40% had a partial response (pR). No patients with a cR had a recurrence whereas one patient with a pR had a local recurrence following ICBT. For the entire cohort, the median follow-up time was 59.9 months (range: 15–153). The estimated 5-year overall survival, disease-specific survival, and local failure-free survival were 67%, 80%, and 90%, respectively. Among survivors, there were no late grade 3–4 toxicities. In this series of patients with small primary early-stage vaginal tumors, long term clinical outcomes were acceptable following RT and MRI-based ICBT, especially among those with a cR at time of brachytherapy., Highlights • Brachytherapy for vaginal cancer is highly individualized. • This small case series included stage I–II patients with limited tumor volume. • A pelvic MRI with vaginal cylinder in place (MRVC) documented tumor extent at diagnosis. • Patients with initial tumor thickness on MRVC ≤ 2 cm received EBRT + intra-cavitary boost. • Best results were among those with no residual disease at time of brachytherapy.

Purpose To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors of outcomes and toxicity. Methods and Materials We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded. Radiation-related acute and late toxicities were recorded. Prognostic variables included performance status, disease site, disease-free interval, chemotherapy, and RT dose and volume. Correlative analyses were performed separately for surgery and nonsurgery patients. Results Two hundred six patients (91%) were retreated with curative intent, and 173 had HNSCC histology; 104 (50%) underwent salvage resection, and 135 (66%) received chemotherapy. Median follow-up after reirradiation was 24.7 months. Clinical outcomes were worse for HNSCC patients, with 5-year locoregional control, progression-free survival, and overall survival rates of 53%, 22%, and 32%, respectively, compared with 74%, 59%, and 79%, respectively, for non-HNSCC patients. On multivariate analysis, concurrent chemotherapy and retreatment site were associated with tumor control, whereas performance status was associated with survival. Favorable prognostic factors specific to surgery patients were neck retreatment and lack of extracapsular extension, whereas for nonsurgery patients, these were a nasopharynx subsite and complete response to induction chemotherapy. Actuarial rates of grade ≥3 toxicity were 32% at 2 years and 48% at 5 years, with dysphagia or odynophagia being most common. Increased grade ≥3 toxicity was associated with retreatment volume >50 cm 3 and concurrent chemotherapy. Conclusions Reirradiation with IMRT either definitively or after salvage surgery can produce promising local control and survival in selected patients with head and neck cancers. Treatment-related toxicity remains significant. Prognostic factors are emerging to guide multidisciplinary treatment approaches and clinical trial design.

Both iodine-125 ((125)I) Collaborative Ocular Melanoma Study and ruthenium-106 ((106)Ru) eye plaques can achieve excellent tumor control in patients diagnosed with uveal melanoma. We analyzed our single institutional experience in the management of ocular melanoma treated with either (125)I or (106)Ru plaque brachytherapy.The records of 107 patients with uveal melanoma treated with either (106)Ru (n = 40) or (125)I (n = 67) plaque brachytherapy between 2000 and 2008 were retrospectively reviewed. Tumor control parameters and toxicity were assessed.Actuarial 5-year rates of local control, progression-free survival, and overall survival with (106)Ru were 97%, 94%, and 92%, respectively. For (125)I, these values were 83%, 65%, and 80%. In the subset of patients with tumor apex height ≤5 mm (36 (125)I and 40 (106)Ru), there was no difference in overall survival; however, progression-free survival was significantly improved with (106)Ru (P = .02). Enucleation-free survival was significantly different between the 2 subsets, with no enucleations in the (106)Ru cohort (P = .02). Patients treated with (106)Ru experienced reduced retinopathy (P = .03) and cataracts (P.01).Both (125)I and (106)Ru eye plaque brachytherapy treatment result in encouraging tumor control for patients with uveal melanoma. We demonstrate that (106)Ru offers these benefits with reduced toxicity in patients treated for uveal melanomas ≤5 mm in apical height.

To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment.Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria.101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy20% (P=.016).Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.

Purpose Palladium-103 ( 103 Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after 103 Pd monotherapy. Methods and Materials Fifty men with intermediate-risk prostate cancer underwent 103 Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests. Results Postimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI ( p = 0.019 for V 100 and p D 90 ). Prostate volumes were smaller on the CT/MRI scans ( p p V 100 and D 90 ). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples. Conclusions CT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after 103 Pd monotherapy implants.

Purpose Current information about the anatomic distribution of lymph node (LN) metastases from cervical cancer is not precise enough for optimal treatment planning for highly conformal radiation therapy. To accurately define the anatomic distribution of these LN metastases, we mapped [ 18 F] fluorodeoxyglucose positron emission tomography (FDG PET)-positive LNs from 50 women with cervical cancer. Methods and Materials Records of patients with cervical cancer treated from 2006 to 2010 who had pretreatment PET/computed tomography (CT) scans available were retrospectively reviewed. Forty-one consecutive patients (group 1) with FDG-avid LNs were identified; because there were few positive paraortic LNs in group 1, 9 additional patients (group 2) with positive paraortic LNs were added. Involved LNs were contoured on individual PET/CT images, mapped to a template CT scan by deformable image registration, and edited as necessary by a diagnostic radiologist and radiation oncologists to most accurately represent the location on the original PET/CT scan. Results We identified 190 FDG-avid LNs, 122 in group 1 and 68 in group 2. The highest concentrations of FDG-avid nodes were in the external iliac, common iliac, and paraortic regions. The anatomic distribution of the 122 positive LNs in group 1 was as follows: external iliac, 78 (63.9%); common iliac, 21 (17.2%); paraortic, 9 (7.4%); internal iliac, 8 (6.6%); presacral, 2 (1.6%); perirectal, 2 (1.6%); and medial inguinal, 2 (1.6%). Twelve pelvic LNs were not fully covered when the clinical target volume was defined according to Radiation Therapy Oncology Group guidelines for intensity modulated radiation therapy for cervical cancer. Conclusions Our findings clarify nodal volumes at risk and can be used to improve target definition in conformal radiation therapy for cervical cancer. Our findings suggest several areas that may not be adequately covered by contours described in available atlases.

Purpose Head and neck (H&N) cancers arising in previously irradiated volumes were rarely treated with radiotherapy due to concerns of toxicity. With improved precision in planning and delivery, reirradiation has been increasingly used. We reviewed our institutional experience using IMRT in the management of previously irradiated H&N carcinoma. Materials and methods The records of 136 patients treated with IMRT reirradiation at U.T. M.D. Anderson Cancer Center for H&N cancer between 1999 and 2012 were retrospectively reviewed. Reirradiation was defined as any overlap between the two radiation treatment volumes. Severe toxicity related to reirradiation included events requiring hospitalization, urgent intervention, or death. Survival estimates were calculated using the Kaplan–Meier algorithm, excluding those patients treated with palliative intent. Results Thirty-three (24%) patients underwent surgical resection and 70 (51%) patients received chemotherapy. Twenty of these patients received radiation with palliative intent. Median time interval between initial radiation and reirradiation was 23 months. Median follow-up after reirradiation was 33 months. Median reirradiation dose was 60 Gy (range 15–70 Gy), while the median cumulative radiation dose was 120 Gy. The 2- and 5-year overall survival and locoregional control rates were 58% and 63%, and 39% and 51%, respectively. Re-treatment doses ⩾66 Gy trended towards improved LRC ( p = 0.14). Severe reirradiation related toxicity occurred in 35 patients (26%), including three treatment-related deaths. Severe toxicity did not correlate with total or re-treatment dose but was associated with retreatment volumes >150 cc. Conclusions IMRT yields promising local control and survival outcomes in select patients receiving reirradiation for H&N cancer. However, treatment related toxicity continues to be significant despite the increased conformality of IMRT over 3D conformal radiation. Alternative treatment strategies, including the possible use of stereotactic radiotherapy, to further improve conformality and thereby increase the therapeutic ratio, may be explored in the future.