Rates of Occult Invasive Disease in Patients With Biopsy-Proven Oral Cavity Squamous Cell Carcinoma in Situ.

Importance: The likelihood that an oral cavity lesion harbors occult invasive disease after biopsy demonstrating carcinoma in situ (CIS) is unknown. While de-escalated treatment strategies may be appealing in the setting of CIS, knowing whether occult invasive disease may be present and its association with survival outcomes would lead to more informed management decisions. Objective: To evaluate rate of occult invasive disease and clinical outcomes in patients with oral cavity CIS. Design, Setting, and Participants: This was a retrospective population-based cohort study using the National Cancer Database and included adults with biopsy-proven oral cavity CIS as the first diagnosis of cancer between 2004 and 2020. Data were analyzed from October 10, 2022, to June 25, 2023. Exposures: Surgical resection vs no surgery. Main Outcomes and Measures: Analyses calculated the rate of occult invasive disease identified on resection of a biopsy-proven CIS lesion. Univariate and multivariate logistic regression with odds ratios and 95% CIs were used to identify significant demographic and clinical characteristics associated with risk of occult invasion (age, year of diagnosis, sex, race and ethnicity, oral cavity subsite, and comorbidity status). Kaplan-Meier curves for overall survival (OS) were calculated for both unresected and resected cohorts (stratified by presence of occult invasive disease). Results: A total of 1856 patients with oral cavity CIS were identified, with 122 who did not undergo surgery (median [range] age, 65 [26-90] years; 48 female individuals [39.3%] and 74 male individuals [60.7%]) and 1458 who underwent surgical resection and had documented pathology (median [range] age, 62 [21-90] years; 490 female individuals [33.6%] and 968 male individuals [66.4%]). Of the 1580 patients overall, 52 (3.3%) were Black; 39 (2.5%), Hispanic; 1365 (86.4%), White; and 124 (7.8%), other, not specified. Among those who proceeded with surgery with documented pathology, 408 patients (28.0%) were found to have occult invasive disease. Higher-risk features were present in 45 patients (11.0%) for final margin positivity, 16 patients (3.9%) for lymphovascular invasion, 13 patients (3.2%) for high-grade invasive disease, and 14 patients (3.4%) for nodal involvement. For those patients with occult disease, staging according to the American Joint Committee on Cancer's AJCC Cancer Staging Manual, eighth edition, was pT1 in 341 patients (83.6%), pT2 in 41 (10.0%), and pT3 or pT4 disease in 26 (6.4%). Factors associated with greater odds of occult invasive disease at resection were female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite. With median 66-month follow-up, 5-year OS was 85.9% in patients who proceeded with surgical resection vs 59.7% in patients who did not undergo surgery (difference, 26.2%; 95% CI, 19.0%-33.4%). Conclusions and Relevance: This cohort study assessed the risk of concurrent occult invasion with biopsy-proven CIS of the oral cavity, demonstrating that 28.0% had invasive disease at resection. Reassuringly, even in the setting of occult invasion, high-risk disease features were rare, and 5-year OS was nearly 80% with resection. The findings support the practice of definitive resection if feasible following biopsy demonstrating oral cavity CIS.

Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.

Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer. Patients will be randomized to rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT fraction (5 × 10 Gy). The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity.

The use of high doses of radiation delivered directly to tumors (stereotactic body radiation therapy [SBRT]) may improve survival compared with lower doses of radiation in patients with pancreatic cancer, but it may increase side effects. Rucosopasem, an investigational new drug being developed, can potentially improve the ability of SBRT to treat tumors without decreasing safety. In a previous study, median overall survival was improved when patients were treated with SBRT plus avasopasem, a drug that works the same way as rucosopasem. GRECO-2 is a clinical trial of rucosopasem used in combination with SBRT for treatment of localized pancreatic cancer. Patients will be randomly selected to receive either rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT treatment. The main result being studied is overall survival. Additional results include amount of time before tumors start to grow, how often patients get tumors surgically removed, best overall response and long-term safety. Clinical Trial Registration: NCT04698915 (ClinicalTrials.gov).

Clinical predictors of premature radiotherapy terminations in senior adults with oral cavity and laryngeal carcinoma.

INTRODUCTION: The underlying factors that contribute to early radiotherapy (RT) termination are understudied, especially in the era of hypofractionated treatment regimens. In this retrospective investigation, we examined the characteristics and causes of premature RT terminations in senior adults (>70 years old) with oral cavity (OC) and laryngeal carcinomas. METHODS: Hundred and eighty-eight patients treated with RT ± systemic therapy for OC and laryngeal cancer from 2017 to 2022 were identified. Premature termination was defined as completion of less than 95% of the prescribed RT. Logistic regression analysis was performed to examine factors predictive of premature termination, and survival was determined using the Kaplan-Meier method. RESULTS: Twenty patients (10.6%) experienced premature RT terminations. On regression analysis, ECOG score at initiation of RT was the only covariate studied to be independently associated with premature termination (OR 2.00, 95%CI: [1.21, 3.30], p = 0.007). Three-year overall survival (49.1% vs. 77.3%) was significantly reduced in the termination cohort (p < 0.0001). CONCLUSIONS: This analysis demonstrated over 1 in 10 patients had premature RT termination, which prognosticated inferior survival outcomes. Poor performance status may highlight patients at risk for premature termination and thus identify good candidates for hypofractionated protocols.

Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon's two-stage trial.

INTRODUCTION: Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate. METHODS AND ANALYSIS: This is a phase II, Simon's two-stage trial. Patients have pathologically confirmed HNC and an intended regimen of 70 Gy of radiation with concurrent cisplatin. The protocol is initiated on diagnosis of grade 3 mucositis and consists of 2 weeks of 4 times daily (QID) ketamine mouthwash use. The primary endpoint is pain response defined as a combination of pain score and opioid use. 23 subjects will be enrolled in stage 1. If statistical criteria are met, 33 subjects will be enrolled in stage 2. Secondary endpoints include daily pain, daily opioid use, dysphagia at baseline and completion, nightly sleep quality, feeding tube placement and any unscheduled treatment breaks. ETHICS AND DISSEMINATION: All trial data will be stored in an Institutional Review Board (IRB) approved database. The protocol is registered under Northwell IRB registration number #22-0292 and U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval has been granted under IND number 161609. Results are intended to be published in an open-source journal and further data, statistics and source documents are available on request. TRIAL REGISTRATION NUMBER: NCT05331131.

Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Automated health chats for symptom management of head and neck cancer patients undergoing radiation therapy.

OBJECTIVE: To report the early experience using an automated chatbot (Chats)for patient-reported outcomes (PRO) and symptom self-managementinhead and neck cancer (HNC) patients undergoing radiation treatment (RT). METHODS: Patients aged ≥ 18 yearsdiagnosed with HNC who were scheduled to begin RT were given the option to use Chats from June 2018 to June 2019. Enrolled patients received chat notifications two days before weekly on-treatment visitsand every 1-4 weeks after RT for an additional 4 months. After the first in-person follow-up visit, participants completed an electronic usability and satisfaction questionnaire. RESULTS: Of 95 patients who agreed to participate, 84 were eligible for analysis.Participantswere significantly younger than patients who declined participation (mean age 61.3 vs 68.3 years;p-value < 0.001). Patient engagement with Chats was highest at 67% during the first month and declined over time (p-value = 0.004). Concordance between PRO and clinician-reported outcomes (CRO) was fair, ranging from 0.10 to 0.43 (Cohen κ statistics). The most commonly under-reported symptoms were salivary duct inflammation (53%), xerostomia (41%), and mucositis (37%). 89% (39 of 44) of patients who completed surveys found Chats easy to use, and 61% reported that Chats helped with symptom self-management and reduced the need to call the care team. CONCLUSIONS: These early results suggest that an interactive chatbot is feasible and provides support for HNC patients during and after RT. Chats identified discordance between PRO and CRO. Further study is required to measure benefits of Chats in a larger population.

New Potential Options for SBRT in Pancreatic Cancer.

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for patients with pancreatic cancer, as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation (CRT). The objective of this review is to present alternative clinical settings in which SBRT may benefit patients with pancreatic cancer. These include palliation of pain, elderly patients who are not surgical candidates, local therapy in oligometastatic cases and salvaging local failures after surgery or external beam radiation. We will review these individually and provide supporting literature for each.

Patterns of alcohol use among early head and neck cancer survivors: A cross-sectional survey study using the alcohol use disorders identification test (AUDIT).

OBJECTIVE: Alcohol use among survivors of head and neck cancer (HNC) negatively impacts patient outcomes and is an important risk factor for recurrent and second primary tumors. Despite recommendations from several cancer societies, alcohol consumption remains a common problem in this population. METHODS: A cross-sectional study was performed with the Alcohol Use Disorders Identification Test (AUDIT) Self-Report questionnaire. Patients with HNC completed surveys at pre-treatment and follow-up appointments every 3-6 months for at least 2-years after treatment. RESULTS: 796 surveys were available for analysis. Most participants were male (75.7%) and had either oropharyngeal (34.5%) or laryngeal (16.7%) cancer. The percentage of alcohol drinkers decreased from 56.1% at pre-treatment to 40.4% at 0-3 months post-treatment, but then increased and surpassed baseline levels by 24 + months post-treatment (64.4%, p = 0.0079). Concurrently, moderate drinkers (AUDIT = 1 - 3) decreased from 34.2% at pre-treatment to 25.2% at 0-3 months post-treatment, but then increased and surpassed baseline levels at 24 + months post-treatment (39.7%, p = 0.0129). Trends among heavy (AUDIT > 3), and heaviest (AUDIT > 6) drinkers were similar, but not statistically significant. At 24 + months post-therapy, we observed a statistically significant increase in female users (39.1% to 63.2%, p = 0.0213) and moderate drinkers < 55 years old (43.4% to 61.9%, p = 0.0184). CONCLUSION: Alcohol consumption in survivors of HNC transiently decreases in the immediate months after treatment, but then increases and remains largely stable by 24 months. This pattern is particularly concerning and highlights the need for timely interventions.

Subtotal Resection Followed by Adjuvant Radiosurgery for Large Vestibular Schwannomas: Outcomes with Regard to the Timing and Regimen of Irradiation.

OBJECTIVE: To evaluate the results of combined management of large vestibular schwannomas (VS) with initial subtotal resection (STR) followed by adjuvant stereotactic radiosurgery (SRS), with a particular emphasis on the timing and regimen of irradiation. METHODS: Seventeen patients underwent STR of a VS followed by SRS, whereas five others were observed after STR. Early SRS (<6 months after surgery) and late SRS (>6 months after surgery) were done in 8 and 9 patients, respectively. Single- and multisession SRS treatments were administered in 10 and 7 patients, respectively. The mean follow-up durations after surgery and SRS were 40 and 28 months, respectively. RESULTS: The rates of radiological and oncological tumor control after SRS were 82% and 100%, respectively. The tumor volume at the last follow-up and its relative changes after SRS did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). In no patient who was observed after STR of a VS was tumor regrowth noted during a mean follow-up period of 49 months. At 12 months after surgery, motor function of the ipsilateral facial nerve corresponded to House-Brackmann grades I, II, III, and IV in 16 patients (73%), 3 patients (14%), 1 patient (5%), and 2 patients (9%), respectively. Facial nerve function at the last follow-up did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). CONCLUSION: The combination of initial STR followed by adjuvant SRS is an effective treatment strategy for patients with a large VS. Although the optimal timing and regimen of postoperative irradiation of the residual lesion should be defined further, our preliminary data suggest that either early or late SRS after surgery may provide good tumor control and optimal functional results.

Computed tomography-based flap brachytherapy for non-melanoma skin cancers of the face.

PURPOSE: Non-melanoma skin cancers of the face are at high-risk for local recurrence and metastatic spread. While surgical interventions such as Mohs microsurgery are considered the standard of care, this modality has the potential for high rates of toxicity in sensitive areas of the face. Catheter flap high-dose-rate (HDR) brachytherapy has shown promising results, with high rates of local control and acceptable cosmetic outcomes. MATERIAL AND METHODS: Patients with non-melanoma skin cancers (NMSC) located on the face were treated with 40 Gy in 8 fractions, given twice weekly via catheter flap HDR brachytherapy. Clinical target volume (CTV) included the visible tumor plus a margin of 5 mm in all directions, with no additional planning target volume (PTV) margin. RESULTS: Fifty patients with 53 lesions on the face were included, with a median follow-up of 15 months. All were considered high-risk based on NCCN guidelines. Median tumor size and thickness were 18 mm and 5 mm, respectively. Median PTV volume and D90 were 1.7 cc and 92%, respectively. Estimated rate of local control at twelve months was 92%. Three patients (5%) experienced acute grade 2 toxicity. Two patients (4%) continued to suffer from chronic grade 1 skin toxicity at 12 months post-radiotherapy (RT), with an additional two patients (4%) experiencing chronic grade 2 skin toxicity. Forty-nine lesions (92%) were found to have a good or excellent cosmetic outcome with complete tumor remission. CONCLUSIONS: CT-based flap applicator brachytherapy is a valid treatment option for patients with NMSC of the face. This modality offers high rates of local control with acceptable cosmetic outcomes and low rates of toxicity.

Dental radiation dosimetric maps from intensity-modulated radiation therapy planning for head and neck cancers.

BACKGROUND: The purpose of this study was to create dental radiation maps to calculate the mean dose to individual teeth, maxilla and mandible using intensity-modulated radiation therapy (IMRT). METHODS: Eighteen common clinical settings were chosen. Radiation plans were extracted, and each tooth was contoured at its junction with the gingiva and labeled based on the Universal/American numbering system. RESULTS: All patients were treated with prescribed doses of 50-70 Gy in 1.66-2 Gy/fraction. Patients receiving mean doses >50 Gy to the teeth, mandible, and maxilla included those with advanced tumors of the oral cavity and gross lymphadenopathy of level 1b. CONCLUSION: We believe this to be the first study generating dosimetric maps of estimated doses to each tooth and each third of the mandible and the maxilla for common examples of head and neck cancer faced by radiation oncologists. Adoption of these dental maps may help improve clinical workflow efficiency.

Primary extradural tumors of the spinal column: A comprehensive treatment guide for the spine surgeon based on the 5th Edition of the World Health Organization bone and soft-tissue tumor classification.

BACKGROUND: In 2020, the World Health Organization (WHO) published the 5th version of the soft tissue and bone tumor classification. Based on this novel classification system, we reviewed the current knowledge on all tumor entities with spinal manifestations, their biologic behavior, and most importantly the appropriate treatment options as well as surgical approaches. METHODS: All tumor entities were extracted from the WHO Soft-Tissue and Bone Tumor Classification (5th Edition). PubMed and Google Scholar were searched for the published cases of spinal tumor manifestations for each entity, and the following characteristics were extracted: Growth pattern, ability to metastasize, peak age, incidence, treatment, type of surgical resection indicated, recurrence rate, risk factors, 5-year survival rate, key molecular or genetic alterations, and possible associated tumor syndromes. Surgical treatment strategies as well as nonsurgical treatment recommendations are presented based on the biologic behavior of each lesion. RESULTS: Out of 163 primary tumor entities of bone and soft tissue, 92 lesions have been reported along the spinal axis. Of these 92 entities, 54 have the potential to metastasize. The peak age ranges from conatal lesions to 72 years. For each tumor entity, we present recommended surgical treatment strategies based on the ability to locally destruct tissue, to grow, recur after resection, undergo malignant transformation as well as survival rates. In addition, potential systemic treatment recommendations for each tumor entity are outlined. CONCLUSION: Based on the 5th Edition of the WHO bone and soft tumor classification, we identified 92 out of 163 tumor entities, which potentially can have spinal manifestations. Exact preoperative tissue diagnosis and interdisciplinary case discussions are crucial. Surgical resection is indicated in a significant subset of patients and has to be tailored to the specific biologic behavior of the targeted tumor entity based on the considerations outlined in detail in this article.

Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8.

PURPOSE: Management of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire. MATERIALS AND METHODS: 171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4-6 weeks, and at 2-3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as 'vulnerable', 11-14 as 'intermediate', and >14 as 'fit'. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes. RESULTS: Median follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were 'vulnerable', 37% were 'intermediate', and 12% were 'fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001). CONCLUSION: The G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.

Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer.

BACKGROUND AND PURPOSE: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. MATERIALS AND METHODS: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control. RESULTS: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. CONCLUSIONS: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice. TRIAL REGISTRATION: Northwell Health Protocol #09-309A (NCT02703493) ( https://clinicaltrials.gov/ct2/show/NCT02703493 ).

Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Improving post-CRT neck assessment in patients with HPV-associated OPSCC (Review).

The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

Stereotactic body radiotherapy as primary treatment for elderly and medically inoperable patients with head and neck cancer.

BACKGROUND: Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity. METHODS: A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35-40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions. RESULTS: Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity. CONCLUSION: SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL.

Identifying patterns of failure and secondary primary malignancies in HPV-related oropharyngeal squamous cell carcinomas.

Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

A Model-Based Method for Assessment of Salivary Gland and Planning Target Volume Dosimetry in Volumetric-Modulated Arc Therapy Planning on Head-and-Neck Cancer.

This study examined the relationship of achievable mean dose and percent volumetric overlap of salivary gland with the planning target volume (PTV) in volumetric-modulated arc therapy (VMAT) plan in radiotherapy for a patient with head-and-neck cancer. The aim was to develop a model to predict the viability of planning objectives for both PTV coverage and organs-at-risk (OAR) sparing based on overlap volumes between PTVs and OARs, before the planning process. Forty patients with head-and-neck cancer were selected for this retrospective plan analysis. The patients were treated using 6 MV photons with 2-arc VMAT plan in prescriptions with simultaneous integrated boost in dose of 70 Gy, 63 Gy, and 58.1 Gy to primary tumor sites, high-risk nodal regions, and low-risk nodal regions, respectively, over 35 fractions. A VMAT plan was generated using Varian Eclipse (V13.6), in optimization with biological-based generalized equivalent uniform dose (gEUD) objective for OARs and targets. Target dose coverage (D 95, D max, conformity index) and salivary gland dose (D mean and D max) were evaluated in those plans. With a range of volume overlaps between salivary glands and PTVs and dose constraints applied, results showed that dose D 95 for each PTV was adequate to satisfy D 95 >95% of the prescription. Mean dose to parotid <26 Gy could be achieved with <20% volumetric overlap with PTV58 (parotid-PTV58). On an average, the D mean was seen at 15.6 Gy, 21.1 Gy, and 24.2 Gy for the parotid-PTV58 volume at <5%, <10%, and <20%, respectively. For submandibular glands (SMGs), an average D mean of 27.6 Gy was achieved in patients having <10% overlap with PTV58, and 36.1 Gy when <20% overlap. Mean doses on parotid and SMG were linearly correlated with overlap volume (regression R 2 = 0.95 and 0.98, respectively), which were statistically significant (P < 0.0001). This linear relationship suggests that the assessment of the structural overlap might provide prospective for achievable planning objectives in the head-and-neck plan.

Quality of Life Outcomes Following Organ-Sparing SBRT in Previously Irradiated Recurrent Head and Neck Cancer.

Purpose: To present a retrospective analysis of the efficacy, toxicity, and quality of life (QoL) of patients treated with OAR Extreme -sparing stereotactic body radiotherapy (SBRT) in previously-irradiated head and neck cancer. Materials/Methods: From 11/2012 to 7/2015, 60 patients with in-field recurrence of head and neck cancer underwent re-irradiation with SBRT. Retreatment sites included the aerodigestive tract (43%), lateral neck (22%), and skull base (35%). The median prior RT dose was 63.6 Gy with a median time from prior irradiation of 16.5 months. The median volume treated was 61.0 cc. Patients were treated with 40 Gy in the definitive setting or 35 Gy in the post-operative setting in five fractions. Dose constraints to the OAR Extreme were calculated with a BED calculator using an alpha/beta ratio of 3 to reduce the risk of late toxicities. QoL data was collected from patients at the time of consultation and at subsequent follow up appointments using the MD Anderson Dysphagia Inventory (MDADI) and Symptom Inventory (MDASI). Results: The 1- and 2- year rates of local, regional, and distant control and overall survival were 79/79, 74/70, 74/71, and 59/45%, respectively. Late grade 3 toxicities were seen in 3% in the group treated to the aerodigestive tract and 1% in the group treated to the skull base. No grade 4 or 5 toxicities were observed. Patients with skull base re-irradiation maintained a stable QoL score after radiation treatment, while patients treated to the aerodigestive tract demonstrated a slight impairment associated with worsening dysphagia, compared to their pretreatment baseline. All groups experienced an increase in xerostomia. Conclusions: OAR Extreme -sparing SBRT is able to achieve excellent tumor coverage while protecting the organs at highest risk of re-irradiation-related complications. The potential for lower toxicities and maintained QoL with this treatment makes it a promising option for salvage of recurrent head and neck cancer. SUMMARY: Local control and overall survival rates for recurrent head and neck cancer remain poor, despite the use of local therapy. In addition, re-irradiation with conventional radiation therapy confers a high rate of grade 3 and higher late toxicities. SBRT appears to improve the therapeutic ratio in this patient population, and treatment planning with a focus on sparing OAR Extreme may further decrease the rates of morbidity in these patients.