Quad Shot Research Articles

Retrospective Review of the Safety of Osimertinib with Thoracic Radiotherapy

<h3>Purpose/Objective(s)</h3> Tyrosine Kinase inhibitor [TKI] therapy is the backbone of treatment for patients who progress after definitive treatment for EGFR mutated non-small cell lung carcinoma [NSCLC], or those who are diagnosed with metastatic disease. Evidence from phase II and III clinical trials have suggested that ablative consolidation of oligometastatic or progressive sites leads to improved progression-free, and overall survival. For patients on TKI therapy, there is little information regarding the safety of combining therapy with radiation therapy [RT]. There are 5 FDA approved EGFR TKI's but simertinib is most used today and is the focus of this review. We present the risk of toxicity of concurrent simertinib and thoracic RT in a large institutional cohort. <h3>Materials/Methods</h3> A prospectively collected database of patients treated with simertinib from September 2014 through March of 2021 was reviewed to identify those who had RT at some point in their treatment. 206 individual patients were identified of whom 60 had treatment directed to a thoracic target. 13 patients were treated to 2 metachronous thoracic sites yielding 73 individual treatments. Patient records were retrospectively reviewed to identify practice patterns regarding sequencing of RT and TKI, and the incidence of toxicity. <h3>Results</h3> In these 73 targets, most volumes were treated with SBRT [3-5 fractions] 42(57%). Twenty-one targets (29%) were treated with hypofractionation [8-20 fractions; HFRT], 8(11%) were treated with conventional radiation, [200cGY per fraction; CFR] and 2 with quad shot fractionation [QS]. The median PTV size was 91.25cc (range 8.55cc – 767.95cc). In 43 treatments radiation was delivered concurrently with simertinib, drug was held for 20 radiation treatments, and 10 treatments were delivered before simertinib initiation. Of those tumors treated with continuous simertinib dosing, 28 tumors were treated with SBRT, 13 with HFRT, 1 CFR and 1 with QS. 24 patients were diagnosed with radiation pneumonitis following thoracic RT; 4/11(36%) tumors treated prior to TKI; 6/20(30%) treatments when medication was held; and 14/44(32%) tumors when simertinib was continued through radiation (p=0.14). Most cases of pneumonitis were grade 1-2 and only 2 patients developed grade 3 pneumonitis. Grade 3 pneumonitis was not associated with continuous simertinib dosing. The median PTV for any grade pneumonitis was 112.27cc. Institutional V20 planning constraints were met in all but 1 patient who was treated with CFR. Other toxicities reported included 7 events of esophagitis, and 4 events of dermatitis all of which were grade 1-2. <h3>Conclusion</h3> Patients receiving osimertininb concurrently with thoracic RT did not appear to have higher rates of pneumonitis relative to those who held drug during RT or initiated it after RT. This suggests it is safe to continue simertinib concurrently with thoracic RT when standard planning dose limits are followed.

Neoadjuvant QUAD shot for downstaging or temporizing locally advanced oral cavity cancer prior to definitive surgery

ObjectivesThe mainstay of oral cavity cancer treatment is surgery, often with adjuvant therapies. However, patients often present with locally advanced disease and downstaging would render surgery more feasible. We evaluated hypofractionated radiation therapy (QUAD Shot) prior to definitive surgery for head and neck cancers, with a goal of downstaging. Materials and MethodsEighteen patients with primary head and neck malignancy, predominantly locally advanced oral cavity cancers, received QUAD Shot radiation therapy from June 2016 to July 2021. External beam radiation therapy was delivered to the primary lesion in four fractions over two days, two fractions/day at least six hours apart with total dose ranging from 1400 cGy to 1500 cGy. Twelve patients proceeded to definitive surgery. ResultsOf the twelve patients receiving surgery, one had complete response to radiation therapy with no pathological disease seen at surgery. Four patients had a partial response, defined as downstaging on final pathology. Five patients showed no response, and two had progressive disease defined as upstaging on final pathology. Seven patients had radiographic primary tumor shrinkage ≥ 0.5 cm following Quad Shot. The Quad Shot was tolerated well with no reported adverse effects. ConclusionDiscrepancies between clinical- and pathological-staging are common and expected. However, ∼40 % of our patients experienced downstaging following QUAD Shot. Thus, neoadjuvant radiation therapy may be viable for temporizing tumor growth while awaiting surgery, or for downstaging and thus facilitating more technically feasible and less morbid surgery for locally advanced head and neck cancers.

Neoadjuvant QUAD Shot as Temporizing Measure Prior to Definitive Surgery for Locally Advanced Oral Cavity Cancer

<h3>Purpose/Objective(s)</h3> The mainstay of treatment for oral cavity cancer is surgery, often with adjuvant therapies if necessary. However, given issues involving prolonged workup or scheduling of surgery, treatment delays are inevitable. We aim to evaluate the utilization of a temporizing hypofractionated course of radiation therapy in the form of a Quad Shot prior to planned surgery for head and neck cancers. <h3>Materials/Methods</h3> Eighteen patients with a primary head and neck malignancy, predominantly locally advanced oral cavity cancers, received radiation therapy in the form of a Quad Shot from June 2016 to July 2021. External beam radiation therapy was delivered to the site of primary disease over 2 days, with 2 fractions per day given at least 6 hours apart. Total dose delivered ranged from 1400cGy to 1500cGy. Out of the 18 patients, 12 (66.7%) went on to receive surgery. The remaining patients either passed away prior to planned surgery or went on to receive definitive chemoradiation or palliation. American Joint Committee on Cancer (AJCC) clinical and pathological stage groups were recorded for each patient. <h3>Results</h3> Out of the 12 patients who received surgery, 1 patient (5.6%) had complete response to the dose of temporizing radiation with no pathological disease seen at surgery. Four patients (22.2%) had a partial response as defined as downstaging on final pathology. No response was seen in 11 patients (61.1%), and 2 patients (11.1%) had progression of disease as defined as upstaging on final pathology. The Quad Shot was overall well tolerated with no recorded adverse effects. Eight patients (44.4%) received adjuvant radiation +/- chemotherapy following surgery. <h3>Conclusion</h3> Discrepancies between clinical staging and pathological staging are common and expected. However, a quarter of our patients experienced downstaging following a temporizing Quad Shot. This raises the question of whether neoadjuvant radiation therapy is a viable option to temporize tumor growth while awaiting a surgery for head and neck cancers.

Use of a cyclical hypofractionated radiotherapy regime ('QUAD shot') for the treatment of feline sinonasal carcinomas.

Radiation therapy is the treatment of choice for cats with sinonasal carcinomas. Different protocols have been described in the literature, though a clear consensus regarding the optimal protocol is lacking. The aim of the study was to describe the tolerability, efficacy and outcome of cats treated with a cyclical hypofractionated protocol. Cats with histologically diagnosed sinonasal carcinomas in a single institution were retrospectively included. All patients were treated with a cyclical hypofractionated protocol ('QUAD shot' regime). Cats were treated with 4 Gray (Gy) delivered in four fractions within 48 h, with a minimum of 6 h between two treatments, and repeated every 3-4 weeks for a total dose of 48 Gy in three cycles. Seven cats met the inclusion criteria. Nasal discharge and sneezing were the most common presenting complaints. All cats presented with advanced stage of disease with CT examination (three with modified Adams stage 3 and four with stage 4). Clinical improvement was seen in six cats. Five cats had a follow-up CT; one had a complete response, two had partial responses, one had stable disease and one had progressive disease. Two cats were still alive at the time of writing while four were euthanased owing to tumour-related causes. The median overall survival time was 460 days. The 1-year survival time was 80% and the 2-year survival time was 0%. Severe acute or late toxicity was not reported. This is the first report of a cyclical hypofractionated protocol in the veterinary literature that can provide prolonged survival in cats with advanced stage sinonasal carcinoma. Its use should be considered in patients when prolonged hospitalisation can be detrimental to quality of life, while still delivering a therapeutic total dose of radiation therapy.

Tumor control after palliative hypofractionated, "Quad-shot," external beam radiotherapy followed by brachytherapy: An effective approach in medically compromised and/or elderly patients with cervix cancer.

Cervix cancer is still a leading cause of death in developing countries. Concurrent chemoradiation (CCRT) over 5 weeks followed by brachytherapy is standard of care in locoregionally advanced cervix cancer. Such prolonged treatment may not be tolerated in medically compromised patients. High-dose interrupted hypofractionated Quad-Shot (QS) radiotherapy with brachytherapy treatment was well tolerated. This study aims to assess the locoregional tumor control in cervix cancer patients who were treated with QS regimen. Retrospective. Newly diagnosed histologically confirmed cervix cancer patients who were unfit for conventional CCRT and who were treated with QS protocol between 1999 and 2016 were analyzed. Tumor stage, treatment, and follow-up details were retrieved from an ethics-approved prospective departmental database. Descriptive statistics and Kaplan-Meier method were used for estimating survival. Thirty-six patients were available for analysis. The median age was 70.5 (32-92) years. Twenty-two of 36 (61.1%) patients had nodal disease while 33% of all patients had distant metastasis. Of 27 patients who died during follow-up, the local and pelvic control was 75% and 60%, respectively. The median overall survival and progression-free survival were 18.6 months. Grade 3-4 toxicity was observed (16%) in the bowel only. Hypofractionated QS radiotherapy with brachytherapy resulted in an overall 82.1% at least stable disease at the primary site. This treatment regimen was well tolerated and may be considered appropriate for patients who may not be suitable for conventional fully fractionated CCRT.

Rapid and Durable Symptom Palliation With Quad Shot Radiation Therapy to Nonosseous Metastatic/Recurrent Cancer in Elderly or Frail Patients in a Rural Community Clinic

More than half of patients with cancer receiving radiation therapy (RT) are treated in a palliative setting. Elderly or frail patients with metastatic/recurrent cancer require palliative RT that can provide a rapid cancer-related symptom response with low toxicity and short overall treatment time. Cyclical hypofractionated RT (quad shot: 14-14.8 Gy/4 fractions, twice-daily treatments with 6-hour intervals on 2 consecutive days monthly to a total of 42-44.4 Gy) can be a practical palliative RT regimen for patients with poor performance status. In this report, we present palliative symptom response and objective tumor response after quad shot for elderly or frail patients with nonosseous metastatic/recurrent cancers in various sites with varying histology.

Proton radiotherapy for recurrent or metastatic sarcoma with palliative quad shot.

Patients with previously treated, recurrent or metastatic sarcomas who have progressed on multiples lines of systemic therapy may have limited options for local control. We evaluated outcomes of palliative proton therapy with the quad shot regimen to unresectable disease for patients with recurrent and/or metastatic sarcoma. From 2014 to 2018, 28 patients with recurrent or metastatic sarcomas were treated to 40 total sites with palliative proton RT with quad shot (14.8 Gy/4 twice daily). Outcomes included toxicity, ability to receive further systemic therapy, and subjective palliative response. Univariate analysis was performed for local progression‐free survival (LPFS) and overall survival (OS). Of the 40 total sites, 25 (62.5%) received ≥3 cycles with median follow up of 12 months (IQR 4–19). The most common histologies were GIST (9; 22.5%) and leiomyosarcoma (7; 17.5%). A total of 27 (67.5%) sites were located in the abdomen or pelvis. Seventeen (42.5%) treatments involved concurrent systemic therapy and 13 (32.5%) patients received further systemic therapy following proton therapy. Overall subjective palliative response was 70%. Median LPFS was 11 months and 6‐month LPFS was 66.1%. On univariate analysis, receipt of four cycles of quad shot (HR 0.06, p = 0.02) and receipt of systemic therapy after completion of radiation therapy (HR 0.17, p = 0.02) were associated with improved LPFS. Three grade 3 acute toxicities were observed. The proton quad shot regimen serves as a feasible alternative for patients with previously treated, recurrent or metastatic sarcomas where overall treatment options may be limited.

Head And Neck Quad Shot Using CT Based Adaptive Treatment On A Ring Gantry LINAC

The head and neck (HN) quad shot (QS) regimen entails three cycles of four fractions given BID for two days, with 3-4 weeks between cycles. The current workflow requires patients to come in before each cycle for an additional CT simulation to determine whether the current plan is suitable or if a new plan is required. Here we propose an alternative workflow with a commercially available CBCT-guided online adaptation platform coupled with ring gantry LINAC and determine the feasibility of online adaptation at the beginning of each new cycle for HN QS patients. Three HN patients were planned with the QS regimen on the initial CT simulation. Adapted workflow was simulated using CBCT images acquired with C-arm or the ring gantry LINAC. Each step in the adapted workflow was timed and artificial intelligence (AI) guided automatic contours were graded as needing no edits, minor edits, or major edits by a physician. The initial plan (scheduled) is calculated utilizing the CBCT image of the treatment day, and an adapted plan is optimized and calculated. The physician decided whether to continue with the scheduled plan or use the newly adapted plan for the entire cycle. The total time to an approved plan was recorded. Five fractions were successfully simulated for three patients. The table below shows the origin of the CBCT utilized as well as the time (in minutes) for each step of the adapted workflow. Only one fraction needed major edits on any of the automated contours, the target contour from the C-arm LINAC CBCT. This is likely due to the inferior image quality to that of the ring gantry’s CBCTs. The best image quality as noted by the physician was the Pelvis Large Fast protocol with breath hold (25 second scan time). On average, the physician spent 3.5 minutes reviewing and editing all contours. The average time to get an approved plan was 11.2 minutes. For patients 1 and 2, the original scheduled plan was determined suitable to continue using. For patient 3, the adapted plan had improved quality over the scheduled plan due to patient weight loss. An adaptive workflow for the first fraction of each cycle for head and neck quad shot regimen has been shown to be feasible. With automated contouring and planning, an adapted plan can be created in under 15 minutes. This workflow would obviate the need for additional CT simulations resulting in less travel burden for patients receiving palliative therapy and reduce CT simulation workload.Abstract 3972; TablePatientCBCTProtocolAI OAR auto contours time (min)MD OAR review/edits (min)AI Target auto-contour time (min)MD target review/edits (min)Plan computationPlan ReviewApproved plan (total min)1C-armHead0.5Minor (2)2Major (4)23Scheduled (15)2Ring-gantryHead1none (0.5)3none (3)12Scheduled (11)2Ring-gantryPelvis Large Fast1none (0.5)2none (1)0.53Scheduled (9)3Ring-gantryPelvis Large Fast – breath hold1Minor (1)1none (2)22Adapted (12)3Ring-gantryPelvis Large Fast1none (0.5)1Minor (3)21Adapted (9)Average0.90.91.82.61.52.211.2 Open table in a new tab

Palliation of advanced pelvic malignancies via quad shot regimen: A single institution experience

Objective: RTOG 8502 outlines a palliative external beam radiotherapy (EBRT) regimen commonly known as the Quad Shot, wherein cycles of 4 twice-daily treatments are delivered; here our goal is to review techniques used for Quad Shot delivery at our institution and outcomes.

A Prospective Interventional Study to Compare Two Weeks versus Four Weeks Gap in ‘Quad Shot’ Regimen in Locally Advanced Head and Neck Cancers

A Prospective Interventional Study to Compare Two Weeks versus Four Weeks Gap in ‘Quad Shot’ Regimen in Locally Advanced Head and Neck Cancers

English

English

Last-line local treatment with the Quad Shot regimen for previously irradiated head and neck cancers

Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7Gy twice daily over 2 consecutive days at 4weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. Median age was 66years. Median follow-up for all patients was 6.0months and 9.7months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were>2year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1months with 1-year LPFS 17.7%, and median OS was 6.4months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS>70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n=18). No Grade 4-5 toxicities were observed. Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS>70 and proton therapy are associated with survival improvements.

Last-line Local Treatment with the Quad Shot Regimen for Previously Irradiated Head and Neck Cancers

There are guidelines to assist with patient selection for reirradiation in recurrent head and neck (HN) cancer, but those who are ineligible for definitive retreatment often have limited effective or tolerable locally palliative options before hospice. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy for patients with prior HN radiation therapy (RT) who were incurable and ineligible for definitive salvage.

Last-line Treatment with the Quad Shot Regimen for Previously Irradiated Head and Neck Cancers

Last-line Treatment with the Quad Shot Regimen for Previously Irradiated Head and Neck Cancers

Proton Radiotherapy for Recurrent or Metastatic Sarcoma with Palliative Quad Shot and SBRT

Proton Radiotherapy for Recurrent or Metastatic Sarcoma with Palliative Quad Shot and SBRT

PO-149 Impact of Palliative Quad Shot RT on psychosocial outcomes in locally advanced HNC in MLIC’s

PO-149 Impact of Palliative Quad Shot RT on psychosocial outcomes in locally advanced HNC in MLIC’s

Palliative head-and-neck radiotherapy with cyclical hypofractionated radiotherapy (Quad Shot): A single-institutional experience

Background: This study aims to report on our institutional experience of palliative radiotherapy (RT) in the locally advanced head and neck by cyclical hypofractionated RT (Quad Shot) which is a short-course palliative regimen with good patient compliance, low rates of acute toxicity, and good response rates. Objectives: The objectives of the study were to review the use of the Quad Shot technique at our institution to quantify the palliative response in locally advanced head-and-neck cancer. Materials and Methods: Between April 2017 and July 2019, 45 patients with biopsy-proven squamous cell carcinoma of the head-and-neck region at the Department of Radiotherapy, Nil Ratan Sircar Medical College, Kolkata, which were deemed to be fit for palliative RT by departmental tumor board were given cyclical hypofractionated palliative RT as 14 Gy in four fractions over 2 days, twice daily, repeated every 4 weeks for a maximum of 3 cycles. Retrospective assessment was done for improvement in pain and dysphagia and also response to treatment. Results: Pain response occurred in 66.7% of the patients. The mean pain scores decreased significantly from pre- to post-treatment, 47.4 to 21.5 (P < 0.0001). The mean initial dysphagia score improved from 21.9 to 38.2 (P = 0.0002). About 60% of patients developed mucositis (≤ Grade 2), while no Grade 3 mucositis was reported. A total of 30 patients had partial response (66.67%) and 6 patients had stable disease. However, a total of nine patients had progressive disease which included those patients that were given fewer courses of Quad Shot. Conclusion: In locally advanced head-and-neck cancer patients particularly with poor performance status or elderly patients who are in dire need of some form of local therapy for symptom control and palliation, the hypofractionated palliative RT regimen (Quad Shot) offers an effective and quick treatment option which is beneficial both clinically and in logistics issue.

Conventional Fractionation versus Quad Shot in Advanced Head-and-Neck Cancers: A Randomized Controlled Trial.

Context:A significant number of patients with head-and-neck cancers have an incurable disease with limited life expectancy. The objective of the present study was to compare two different short courses of hypofractionated palliative radiotherapy regimens to evaluate symptoms, disease response, and acute toxicity.Materials and Methods:Previously untreated 50 patients of Stage IV B and IV C head and neck cancers were randomized to receive conventional hypofractionated palliative radiotherapy 30 Gy/10 fractions/2 weeks (control group) or Quad Shot regimen (study group) 14 Gy in 4 fractions given twice a day at least 6 h apart for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumor progression.Results:Symptom relief was similar among the two schedules for pain (60.86 vs. 57.17), dysphagia (60.86 vs. 52.17%), and hoarseness (43.85 vs. 38.09%). Overall response (that is partial response and stable disease) was seen in majority (>70%) of the patients in both the groups. Treatment was very well tolerated with no patient experiencing more than Grade 3 toxicity in the control group and Grade 2 toxicity in the study group.Conclusions:Quad Shot regimen is an effective hypofractionated palliative radiotherapy schedule with minimal toxicity, good symptom relief, and response rate as compared to conventionally used regimen (30 Gy/10 fractions/2 weeks).

Survival and QOL Outcomes with Quality Palliative QUAD SHOT Radiotherapy in Advanced Head and Neck Cancer (HNC) – An Alternative Regimen in Low Resource Countries

Survival and QOL Outcomes with Quality Palliative QUAD SHOT Radiotherapy in Advanced Head and Neck Cancer (HNC) – An Alternative Regimen in Low Resource Countries

The Use of “QUAD Shot” in Anal Canal Squamous Cell Carcinoma: A Case Study With Review of the Literature

ContextPatients with locoregional anal carcinoma who do not qualify for standard definitive chemoradiation are candidates for a short course of palliative hypofractionated radiotherapy such as QUAD Shot. MethodsA 57-year-old man with massive locoregional squamous cell carcinoma of the anal canal was treated with QUAD Shot (14.8 Gy in four fractions over two consecutive days) repeated every four weeks for a total of two courses. ResultsHe reported symptomatic relief following each course of radiation. In regard to his first QUAD Shot, his pain was 10/10 in severity at the time of admission and 4/10 at the time of discharge. In regard to his second QUAD Shot, his pain was 8/10 at the time of admission and 0/10 at the time of discharge. He did not experience any treatment-related toxicity. He passed away 15 weeks after the first course. ConclusionQUAD Shot is both efficacious and safe for palliation in patients with anal carcinoma.