TPS3629 Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov identifier: NCT05673148 Clinical trial information: NCT05673148 .
A 68-year-old man presented with a mass on the left side of his neck. A biopsy was performed, and histopathological examination revealed squamous-cell carcinoma that was positive for HPV and overexpressed p16, a tumor-suppressor gene product.
Abstract Background The aim of the study was to update our experience treating patients with glottic carcinoma in situ (CIS) with curative radiotherapy (RT). Methods Fifty patients received continuous‐course RT using once‐daily fractionation. Twenty‐eight (56%) had recurrent or persistent CIS after resection. Median total dose was 63.0 Gy; median dose per fraction was 2.25 Gy. Median follow‐up was 9.6 years for all patients and 8.4 years for survivors. Results After RT, 5 patients (10%) recurred locally; salvage surgery was performed in 4 (1 refused). Five‐year outcomes were as follows: local control, 91%; ultimate local control (including patients successfully salvaged after local recurrence), 100%; ultimate local control with larynx preservation, 93%; local‐regional control, 91%; ultimate local‐regional control, 100%; distant metastases‐free survival, 100%; cause‐specific survival, 100%; and overall survival, 81%. No patient experienced a severe complication. Conclusion RT is an excellent treatment for patients with CIS recurrent after transoral excision and those with previously untreated CIS who are unsuitable for partial laryngectomy.
TPS236 Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG). Clinical trial information: NCT05673148 .
Objective: There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT). Methods: OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020. Results: With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/− skin graft), 49%, vs. rotation or free flap, 71% ( P <0.0001); primary closure (+/− skin graft), 49%, versus free flap without bone, 66% ( P =0.0358); and primary closure (+/− skin graft), 49%, versus free flap with bone, 82% ( P <0.0001). Conclusions: The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery.
Ultrasound enhances recombinant tissue plasminogen activator (rt-PA) thrombolysis via a cavitational mechanism. An ex vivo porcine carotid arterial model incorporating physiologic flow and pressure was developed and stable cavitation promoted for thrombolysis. Aged, retracted whole blood clots were exposed to plasma alone, plasma containing rt-PA (3.15 μg/ml), or plasma with rt-PA and the Definity ultrasound contrast agent (0.31 μl/ml), with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity without ultrasound was 34%, and with ultrasound was 83%, which constituted a significant difference (n = 6, p<0.0001). Without Definity there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 6, p<0.0001). Acoustic stable cavitation nucleated by an infusion of Definity enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. [Work supported by Grant Nos. NIH R01-NS047603 and NIH T32GM063483, the University of Cincinnati Neuroscience Institute, the Albert J. Ryan Foundation Fellowship, and the Rindsberg Memorial Fellowship.]
Pancreatic cancer is a highly aggressive disease with a poor prognosis. The mainstay of curative treatment remains surgical resection. Adjuvant chemotherapy has been clearly shown to improve survival. Yet because local-regional recurrence after surgery is the predominant pattern of failure, chemoradiation is often used as a component of treatment. Despite several prospective, randomized trials evaluating adjuvant chemoradiation, controversy persists as to whether it confers a survival benefit. Here we review the rationale for adjuvant chemoradiation and the results of the major studies evaluating the impact of postoperative radiotherapy on disease control and patient survival.
Head and neck cancer pain is a prevalent problem, and the current opioid crisis has highlighted concerns raised in chronic pain management. This study assessed the characteristics of opioid use in patients undergoing treatment for oropharynx cancer and identified risk factors associated with chronic opioid use.Retrospective cohort study.A study was conducted of 198 eligible patients who underwent radiotherapy as part of their treatment for oropharynx cancer at a single institution from 2012 to 2017. p16/human papillomavirus (HPV) status was determined by pathology report review. Opioid use was recorded. Statistical analysis was performed to assess risk factors for chronic opioid use and effect on overall survival.The average age was 62 years, and the mean follow-up was 38 months. Eighty-three percent of patients had stage III/IV disease, and 73% received chemoradiotherapy. Sixty-nine percent were HPV/p16 positive. Fifty-seven (29%) patients had preexisting chronic pain conditions. Chronic opioid use was observed in 53% of the patients. Age ≤ 62 years (P < .0001), history of depression (P = .0356), p16 negative status (P = .0097), opioid use at pretreatment visit (P = .0021), and presence of a preexisting chronic pain condition at time of diagnosis (P = .0181) were associated with chronic opioid use using univariate analysis. On multivariate analysis, T stage and anxiety/depression were associated with chronic opioid use. Overall survival was worse for patients who had chronic opioid use, but was not significant when recurrence was taken into consideration.More than 50% of the patients treated for oropharynx squamous cell carcinoma in this cohort were chronic opioid users after treatment. Identifying patients at greatest risk for chronic opioid use prior to treatment may help with long-term pain management in this patient population.4 Laryngoscope, 129:2087-2093, 2019.
