Curative-intent Chemoradiation Research Articles

Efficacy of immunotherapy retreatment in patients with non-small cell lung cancer receiving consolidative durvalumab.

8625 Background: The standard of care for patients with stage III, unresectable non-small cell lung cancer (NSCLC) is curative intent chemoradiation followed by durvalumab consolidation. However, most patients progress necessitating further treatment. Although immunotherapy (IO) is the cornerstone of treatment in advanced/metastatic disease, the benefit in patients who received prior durvalumab is unclear. Clinical trials excluded prior IO exposure and current guidelines do not provide specific recommendations. This study aims to characterize the efficacy of post-durvalumab IO treatment. Methods: This was a retrospective cohort study conducted at the University of North Carolina (UNC) Medical Center. Adult patients with unresectable NSCLC who received chemoradiation and consolidative durvalumab followed by subsequent systemic therapy for disease progression between February 2018 to May 2023 were included. Patients were excluded if they received targeted therapy as subsequent systemic treatment. The primary endpoint was real-world progression-free survival (rwPFS) of post-durvalumab treatment. Key secondary outcomes included physician assessed response, overall survival (OS), and subgroup analyses to identify biomarkers which may predict benefit from IO retreatment. Results: A total of 66 patients met inclusion criteria, of which 39 (59%) received subsequent chemotherapy alone and 27 (41%) received IO-containing therapy. Of those who received IO-containing treatments, 18 received chemotherapy plus IO (chemoIO) and 9 received IO alone. Durvalumab was discontinued for therapy completion (chemotherapy: 18%, IO: 26%), disease progression (chemotherapy: 54%, IO: 48%), or side effects (chemotherapy: 26%, IO: 19%). No significant difference was observed between median rwPFS of chemotherapy versus IO-containing therapy (7.0 months vs 5.8 months, respectively; p = 0.9419) or OS (13.0 months vs 12.6 months, respectively; p = 0.5769). Notably, patients in our cohort who received IO alone had a numerically longer rwPFS compared to chemoIO (12.6 months vs 5.8 months, respectively; p = 0.3951), as well as a numerically longer OS (12.6 months vs 6.4 months, respectively; p = 0.8885). Conclusions: This study found that there were no statistically significant differences in median rwPFS or OS between chemotherapy or IO-based regimens following the conclusion of durvalumab consolidation. Interestingly, we observed a numerically improved rwPFS and OS in those who received IO alone compared to chemoIO, which suggests there may be key clinical or molecular features that may help identify patients who benefit from IO therapy. We acknowledge the limitations of this small, retrospective study. The efficacy of IO-based regimens post-durvalumab warrants further investigation in a larger, prospective manner to assess the risks and benefits of IO retreatment.

Impact of quality of life and geographic distance on radiation adherence in patients with locally advanced cervical cancer residing in rural areas.

e13512 Background: The efficacy of curative-intent chemoradiation in treating cervical cancer is intricately tied to patient adherence to treatment protocols, often influenced by quality of life. In many areas of the world, treatment centers are often located far from where patients live. We sought to evaluate the impact of distance from the hospital and the quality of life on radiation adherence, especially for patients in the Country of Georgia. Methods: A prospective study conducted at Todua Clinic, Tbilisi, Georgia, from May 2023 - January 2024, involved locally advanced cervical cancer patients undergoing chemoradiation. The study was reviewed by the Todua Clinic Research Ethics Board. The questionnaire was offered at a baseline, at a radiation consult. Quality of life was assessed using the Functional Assessment of Cancer Therapy–Cervical Cancer Version 4. Distance categories (50-100km, 100-200km, 200-300km) were measured, and patient information was extracted from medical records. Radiation nonadherence was defined as missing ≥2 days of external beam radiotherapy. Inclusion criteria comprised stage II and III cervical cancer, prescribed chemoradiation therapy, and rural residency. Multivariable logistic regression was performed to control for confounding variables. Results: Out of the total 50 patients who were asked to participate, 22 declined (reasons for declining: 35% -no mood, 15% - too tired, 45% - not interested, 5% found questions inappropriate to answer) and 28 (56%) participated. 53% of patients were deemed adherent to the prescribed treatment. Statistical analyses unveiled an intriguing trend where mean adherence rates increased with distance from the hospital. However, the Chi-squared test yielded a p-value of 0.065, indicating a marginal significance. The breakdown of mean adherence rates by distance revealed 30.8% for 50-100 km, 66.7% for 100-200 km, and 83.3% for 200-300 km. Educational levels did not significantly impact treatment adherence, despite lower educational attainment in more distant rural areas. The analysis of Quality of Life (Score S) exhibited a negative coefficient (-0.01639), suggesting a subtle decrease in the likelihood of treatment adherence as Quality-of-Life scores increased. Conclusions: This study unveils the interplay between living distance, Quality of Life, and radiation adherence in locally advanced cervical cancer patients in the Country of Georgia. Our findings are interesting because, unlike in other countries where adherence tends to drop as distance increases, we noticed that adherence rates went up when patients lived farther away. One possible reason for this is that some patients move temporarily to cities like Tbilisi just for their radiation treatment. However, we recognize the need for a larger group of people to make our results more reliable and better understand their significance.

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer.

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan-Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively.

A retrospective chart review of palliative care consultation during curative-intent chemoradiation for head and neck cancer.

e24165 Background: Head and neck cancer (HNC) treatment with chemoradiation therapy (CRT) is highly morbid. Patients develop significant symptoms including severe pain, dysphagia, and malnutrition resulting in poor quality of life (QOL), frequent hospitalizations, and high rates of depression. Although integration of palliative care (PC) teams into the care of incurable cancers has resulted in improved QOL, less is known about its integration into the care of patients receiving curative-intent treatments. We sought to characterize the use of PC during HNC CRT at a single cancer center. Methods: We performed a retrospective chart review of patients who received curative-intent CRT for HNC from 1/2008 to 1/2019 at Fox Chase Cancer Center. We excluded patients with metastatic disease or who participated in a PC intervention study. Data extracted included: demographics, comorbidities, cancer subtypes, human papilloma virus (HPV) status, inpatient admissions, feeding tube use, pain medication usage, and PC referrals throughout CRT. We used parametric and non-parametric statistics for hypothesis testing. Results: A total of 332 patients were included; median age was 60, 73% were male, 57.8% had oropharynx HNC, 10.2% had a history of chronic pain, and 18.9% had a psychiatric diagnosis. At the start of treatment, 38.5% of patients were on opioids for cancer pain or chronic pain, which increased to 90.7% of patients by the end of CRT. Six months after CRT, 30% of patients remained on opioids. 44.7% of patients required a feeding tube and 51.4% were admitted to the hospital. Despite the significant symptomatology, only 64 patients (19.2%) were referred to PC during treatment. The patients referred to PC were more likely to be younger (p=0.002), have an inpatient admission during treatment (p=0.001), a history of a psychiatric disorder (p=0.001) or substance abuse (p=0.003), and less likely to have HPV-related HNC. Conclusions: A large majority of patients receiving CRT for HNC faced significant pain with a high hospitalization rate, yet few had the expertise of PC involved in their care. Those who were referred to PC were more likely to have pre-existing substance use or chronic pain. These data provide strong rationale for the development of standardized, PC-based interventions to help with the symptomatology of HNC treatment to better serve this high needs population. [Table: see text]

Intramuscular injections of human placental extract versus conventional symptomatic approaches in radiation-induced oral mucositis, in patients with head and neck cancers, on definitive chemoradiotherapy - A ray of hope?

Despite the availability of a wide range of agents, no single treatment exists for the management of radiation-induced oral mucositis, in patients, with head and neck malignancies, on radical chemoradiation; a debilitating and limiting sequela. Human placental extract is one option that has been proposed. This study aimed at evaluating the therapeutic benefits of human placental extract (Placentrex) in the management of radiation-induced oral mucositis in patients on curative intent treatment for head and neck cancers with concurrent chemoradiation, and to compare the observations with other conventional approaches. Patients presenting to the Department of Radiation Oncology, of a tertiary cancer care center, with biopsy-proven carcinoma of the oral cavity, oropharynx, and hypopharynx, planned for definitive, curative intent chemoradiation, between January 2020 and June 2021, were recruited for this study. The interventional group received a deep intramuscular injection of 2 ml of Placentrex to the deltoid muscle, once-a-day from the 11th fraction of radiation till completion, on treatment and non-treatment days. The control group received supportive, symptomatic, conventional treatments for mucositis. The response was assessed every week during treatment and at the third and sixth months of follow-up and was compared. The study comprised 26 patients, 15 in the interventional group and 11 in the control group. On completion of treatment, 40% in the interventional arm and 81.82% in the control arm had progressed to grade 2 and 3 mucositis (P < 0.05). Treatment interruption was seen in 13% in the interventional arm and 55% in the control arm (P < 0.001). Results from this study show that human placental extract, injection Placentrex, had a significant effect in decreasing the severity of radiation-induced mucositis and thereby reducing any interruption or delay in treatment when compared to other conventional methods.

Radiation recall pneumonitis: PET/CT findings.

A 63-year-old woman with locally advanced lung cancer (Fig. 1A) who was treated with curative-intent chemoradiation therapy (cisplatin, etoposide and 60 Gy in 30 fractions) developed minimal radiation-induced fibrosis in the irradiated area 12 months after the end of the radiation therapy (Fig. 1B). The patient subsequently received consolidation therapy with durvalumab (anti-programmed cell death ligand-1). Twenty-four months after radiation therapy was administered, she was found to have on computed tomography (CT) a new-onset consolidation in the previously irradiated field (Fig. 1C), with normal appearance of the rest of the lung parenchyma. A transbronchial biopsy did not show signs of local recurrence. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT confirmed a homogeneous mildly hypermetabolic lung consolidation (Fig. 1D), consistent with inflammatory changes. PET/CT did not show any intense FDG focal activity that would suggest lung cancer recurrence. Since the patient was asymptomatic, treatment with durvalumab was not discontinued and a presumptive diagnosis of radiation recall pneumonitis (RRP) was made. Subsequent CT studies showed spontaneous but slow progressive reduction in size of the lung consolidation (Fig. 1E).

Waiting to Operate: The Risk of Salvage Esophagectomy.

To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE). A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy. We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019. SE was defined as esophagectomy performed >90 days after chemoradiation ("for time") and esophagectomy performed for recurrence after curative-intent chemoradiation ("for recurrence"). The odds of postoperative serious complications were assessed by multivariable logistic regression. The relationship between SE and OS and DFS were quantified using Cox regression models. Of 1137 patients identified, 173 (15%) underwent SE. Of those, 61 (35%) underwent SE for recurrence, and 112 (65%) underwent SE for time. The odds of experiencing any serious complication [odds ratio, 2.10 (95% CI, 1.37-3.20); P =0.001] or serious pulmonary complication [odds ratio, 2.11 (95% CI, 1.31-3.42); P =0.002] were 2-fold higher for SE patients; SE patients had a 1.5-fold higher hazard of death [hazard ratio, 1.56 (95% CI, 1.25-1.94); P <0.0001] and postoperative recurrence [hazard ratio, 1.43 (95% CI, 1.16-1.77); P =0.001]. Five-year OS for nonsalvage esophagectomy was 45% [(95% CI, 41.6%-48.6%) versus 26.5% (95% CI, 20.2%-34.8%) for SE (log-rank P <0.001)]. Five-year OS for SE for time was 27.1% [(95% CI, 19.5%-37.5%) versus 25.2% (95% CI, 15.3%-41.5%) for SE for recurrence ( P =0.611)]. SE is associated with a higher risk of serious postoperative complications and shorter DFS and OS.

Development of a Radiomic Signature Derived from Apparent Diffusion Coefficient Maps to Predict Outcomes in Cervical Cancer

<h3>Purpose/Objective(s)</h3> Previous studies have suggested that apparent diffusion coefficient (ADC) values from pretreatment MR are associated with outcomes after definitive chemoradiation in patients with cervical cancer. The purpose of this study was to determine whether radiomic features derived from ADC maps on pretreatment diffusion-weighted MRI are predictive of patient outcomes, and prioritize those individual features into a predictive signature. <h3>Materials/Methods</h3> ADC maps were generated from pretreatment pelvic diffusion-weighted MRIs acquired on a 1.5T MRI simulator for twenty-six patients prior to definitive radiotherapy (RT). All patients were treated with curative intent chemoradiation, including external beam RT and image guided brachytherapy as per the standard of care. Median post therapy clinical follow up time was 67 months, and treatment outcomes were approximated by the results of 3-month post therapy FDG-PET. The clinical endpoint was recurrence-free survival (RFS), defined as death or recurrence of cancer. High risk regions, visually identified as areas of ADC hypointensity, were manually contoured. Quantitative radiomic features characterizing intensity, shape, texture and multiscale wavelet transformations of contoured regions of interest were identified using an unsupervised learning approach. A radiomic signature for RFS was generated using a multivariate Cox model that included the best performing feature from each of the four categories. <h3>Results</h3> Our model identified high and low risk groups based on a radiomic signature that stratified patients by RFS (hazard ratio 4.5, p=0.0016). The features chosen for the signature included the median of voxel intensity, joint entropy of the gray level co-occurrence matrix (GLCM), elongation of the region of interest, and LHH wavelet transform of intensity skewness. The mean receiver-operator curve on 5-fold cross-validation had an area under the curve of 0.83 +/- 0.16. <h3>Conclusion</h3> In this pilot study, we have developed a radiomic signature derived from pretreatment ADC maps of cervix tumors that successfully stratifies this group of uniformly treated patients by RFS. Future work will seek to validate our model on a larger independent data set to determine its predictive value as well as correlate these data with radiomic features from FDG-PET/CT images and RNA-seq data from patient tumor samples.

Trends in IMRT Utilization for Definitive Treatment of Cervical Cancer, 2004-2018

<h3>Purpose/Objective(s)</h3> Intensity-modulated radiation therapy (IMRT) is an advanced radiotherapy technique that delivers conformal radiation to desired targets while minimizing dose to surrounding organs at risk. In the post-operative setting, IMRT is associated with reduced acute and late genitourinary and gastrointestinal side effects for patients with cervical cancer. However, no prospective randomized data exist for the use of IMRT in the setting of definitive treatment of intact cervical cancer. The objective of this study was to identify trends in IMRT use for this population. <h3>Materials/Methods</h3> Patients with stage IB2-IVA cervical cancer diagnosed from 2004-2018 who were treated with curative intent chemoradiation were identified in the National Cancer Database. Patients who underwent primary surgical management, did not receive external beam radiation to the pelvis or received radiation outside the pelvis, or received an unspecified technique or target of radiation were excluded. The primary outcome of interest was utilization of IMRT vs 3D conformal radiotherapy (3D-CRT) over time. A Cochrane-Armitage test was performed to assess trends over time. T-tests, chi-square tests, and multivariable logistic regression with propensity score matching were used to identify factors associated with receipt of IMRT. <h3>Results</h3> Overall, 13,974 patients met inclusion criteria; 4,590 (33%) received IMRT, and 9,384 (67%) received 3DCRT. In this cohort, 65% were non-Hispanic White, 45% were early stage (I-II), 80% were squamous histology, 62% received brachytherapy, and 28% had lymph node involvement. The utilization of IMRT increased from 30% in 2004 to 71% in 2018 (p<0.001). After adjustment for clinical and demographic variables, factors associated with IMRT use were: Hispanic ethnicity (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.0-1.5), treatment in the Western U.S. (aOR 1.4, CI 1.2-1.7) and the Southern U.S. (aOR 1.3, CI 1.1-1.5), living more than 50 miles from the treatment facility (aOR 1.2, CI 1.0-1.5), stage III disease (aOR 1.3, CI 1.1-1.5), and lymph node involvement (aOR 1.4, CI 1.3-1.6). Compared to an academic medical center, patients receiving care at a comprehensive community cancer center were less likely to receive IMRT (aOR 0.66, CI 0.59-0.72). There were no differences in IMRT use by age, insurance, or medical comorbidities. <h3>Conclusion</h3> Despite the lack of prospective efficacy data supporting the use of IMRT in patients with intact cervical cancer, IMRT has dramatically increased over the last fifteen years especially for patients with advanced-stage disease or lymph node involvement. More data on the optimal use of IMRT, including appropriate target volume margins and on-board imaging, are needed.

Radiation Dose, Technique and Use of Brain Radiation on Overall Survival in Patients with Limited-Stage Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> The standard of care for limited-stage small cell lung cancer (LS-SCLC) currently involves concurrent chemoradiation +/- prophylactic cranial irradiation (PCI). Previous research has presented conflicting data regarding the optimal radiation therapy (RT) technique, RT dosage, and impact of brain RT on long term overall survival (OS). This study aimed to explore prognostic factors of OS in LS-SCLC cancer patients using a population-based cohort. <h3>Materials/Methods</h3> Data on all patients diagnosed with LS-SCLC in Ontario, Canada from 2005-2017 was obtained using the Institute for Clinical Evaluative Sciences (IC/ES) Data and Analytic Services. Eligible patients received curative intent chemoradiation, and OS was estimated from a landmark date of 6 months post-diagnosis to avoid survivor bias. Kaplan-Meier methods and Cox regression were used to estimate OS and explore differences between RT dose (40-49, 50-59, 60+ Gy), RT technique (3DCRT, IMRT, VMAT), and use of brain RT (PCI – 25 Gy, whole brain RT – 20 or 30 Gy, other brain RT, no brain RT). Multivariate analyses adjusted for sex, age, income quintile, Charlson comorbidity index, disease stage, prior history of cardiac disease, brain RT dose, and laterality. <h3>Results</h3> A total of 1360 LS-SCLC patients who received chemoradiation were included. Median OS (95% CI) was 18.1 months (16.6-19.4). Higher RT dose had significantly improved OS when compared to 40-49 Gy on univariate analysis (HR=0.83, 0.71-0.95, 60+ Gy), however, this did not persist when adjusting for other prognostic factors on multivariate analysis (HR=0.90, 0.77-1.06, 60+ Gy). The use of whole brain RT was associated with worse OS on both univariate (HR=1.47, 1.24-1.74) and multivariate (HR=1.42, 1.18-1.70) analyses. OS (95% CI) at 5-years for RT dose were 40-49 Gy: 16% (13-19%), 50-59 Gy: 23% (18-29), and 60+ Gy: 20% (16-25). For RT technique, OS (95% CI) at 5-years were 3DCRT: 19% (13-22), IMRT: 18% (13-23), and VMAT: 12% (4-25). Multivariate analyses demonstrated that male sex (HR=1.36, 1.20-1.55), more advanced stage disease (HR=1.35/1.94/3.08/1.67 for stage 2/3/4/Unknown vs 1), and older age were prognostic for worse OS. <h3>Conclusion</h3> Analyses of population-based data demonstrated that male sex, older age, and more advanced disease stage were notable predictors of OS in LS-SCLC. RT dose, when adjusting for other important prognostic variables did not predict for improved OS. However, use of whole brain RT (versus PCI or no PCI) was associated with worse OS. Use of PCI versus no PCI did not influence survival in this cohort, nor did RT technique.

A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation

BackgroundTo analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation.MethodsOne hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed.ResultsThe 1-year death rate for all patients was 29% [95% confidence interval (CI): 23–37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17–15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44–15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66–0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001).ConclusionsThe pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.

Comparison of 2-Weekly Versus 4-Weekly Durvalumab Consolidation for Locally Advanced NSCLC Treated With Chemoradiotherapy: A Brief Report

IntroductionDurvalumab 10 mg/kg every 2 weeks for 1 year after chemoradiation has improved overall survival (OS) in unresectable stage III NSCLC. Subsequently, a 20 mg/kg 4-weekly regimen was approved. The study goal was to compare the efficacy and toxicity of the two regimens. MethodsAll patients with NSCLC treated with curative-intent chemoradiation followed by durvalumab from March 1, 2018 to December 31, 2020 at BC Cancer, British Columbia, Canada were included in this retrospective review. Durvalumab dosing schedule, toxicity, progression, and OS were collected. Comparisons between treatment groups were made using chi-square and independent t tests. Kaplan-Meier curves and log-rank test were used to analyze OS. ResultsA total of 152 patients were included in the 2-weekly group and 53 patients in the 4-weekly group. The median follow-up was 19.7 months and 12.0 months, respectively. The median OS was not reached, but 12-month survival rates were 88.4% versus 85.2% (p = 0.55). Toxicity profiles were similar in terms of sites and severity. ConclusionsThere was no significant difference in efficacy or toxicity between the 2-weekly and 4-weekly durvalumab in this cohort of patients with advanced NSCLC previously treated with curative-intent chemoradiation.

Long term clinical outcomes and associated predictors of progression free survival in anal canal cancer.

Reports of long term clinical outcomes for patients with squamous cell carcinoma (SCC) of the anal canal treated with chemotherapy and intensity modulated radiation therapy (IMRT) are limited. Pre-treatment hematologic variables associated with outcomes remain understudied. We sought to report the long-term clinical outcomes of a cohort of patients treated with definitive chemoradiation (CRT) utilizing helical tomotherapy (HT) IMRT at a single tertiary referral center. We further sought to examine for any correlations between pre-treatment hematologic parameters and progression free survival (PFS). Data from patients with SCC of the anal canal treated with definitive CRT using HT IMRT from 2005 to 2017 were collected. Pre-treatment patient characteristics examined for correlations with PFS included: hemoglobin (Hgb) level, age, diabetes mellitus (DM) status, smoking status, neutropenia, thrombocytopenia, leukopenia, neutrophil/lymphocyte ratio, neutrophil/WBC ratio, lymphocyte/WBC ratio, sex, transplant status, HIV status, Karnofsky performance score, T-stage, and N-stage. Pre-treatment Hgb levels were recorded within two weeks prior to starting CRT. Clinical outcomes, including PFS, were described using the Kaplan-Meier estimator. A multivariable (MVA) Cox model of PFS evaluated the impact of pre-treatment Hgb and diabetes while adjusting for T-stage and age. The median patient age was 57 years old (range, 26-87) and there were 39 females (63.9%) with the remaining patients identifying as males. Median patient follow up was 5.8 years. The PFS was 83% at 5 years. The median pre-treatment Hgb was 13 g/dL. On multivariable analysis (MVA), Hgb ≤10 g/dL (HR: 11.891, 95% CI: 2.649-53.391, P=0.001) and a diagnosis of diabetes mellitus (HR: 4.524, 95% CI: 1.436-14.252, P=0.010) were both significantly associated with a worse PFS. These factors were independent of T-stage and age. Long-term clinical outcomes for patients with SCC of the anal canal treated with definitive CRT are presented. Pre-treatment hemoglobin of ≤10 g/dL and diabetes were both independently associated with worse PFS on MVA. This retrospective data supports further prospective study of the impact of hematologic markers and medical co-morbidities such as DM and their management on clinical outcomes for patients with SCC of the anal canal treated with curative-intent CRT.

The Predictive Value of Post-Treatment PET-CT Imaging for Patients With Curable Anal Canal Cancer

<h3>Purpose/Objective(s)</h3> According to 2020 "NCCN" guidelines, post-treatment positron emission tomography (PET) – computed tomography (CT) imaging of the body is <b>not</b> recommended to predict outcomes of patients undergoing curative intent chemoradiation therapy (CRT) for anal canal cancer. This study used PERCIST (Positron Emission tomography Response Criteria In Solid Tumors) to evaluate CRT response and outcomes for our patient population at a single institution. <h3>Materials/Methods</h3> Our "IRB"-approved anal canal database was queried for patients who have undergone CRT, modified "NIGRO" protocol, for carcinoma of the anal canal. The evaluable patient dataset comprised those with both pre- and post-CRT PET-CT imaging of the body. The primary study endpoint was relapse-free survival (RFS) calculated from date of diagnosis to date of first known appearance of disease or death from any cause. Overall survival (OS) was defined using elapsed time between date of diagnosis and date of death and surviving patients were censored using date of last follow-up. Also, the range and median time to first post-CRT PET-CT imaging was determined. RFS and OS were analyzed using Kaplan-Meier method. Complete response rate (CRR) and objective response rate (ORR) were calculated along with 95% confidence intervals using Fisher's exact method. All tests were two-sided, and statistical significance was considered when <i>P</i> < 0.05. <h3>Results</h3> Out of an initial 392 patients in our database registry, 62 had pre/post-CRT PET-CT imaging from June 2008 until May 2020. There were 18 males and 44 females. The median age at diagnosis was 57.7 years (range: 38-84 years). "AJCC" (7^th edition) staging distribution was as follows: 3 Stage I, 13 Stage II, 41 Stage III, and 5 Stage IV. The median total dose of external beam irradiation was 54 Gy (range: 45-60 Gy). Time to post-CRT PET-CT imaging ranged from 0.2 to 27.8 months (mos) [median: 2.9 mos]. Respective PET-response rates regarding primary tumor (N = 62); largest groin node (N = 33); and largest pelvic node (N = 39) were as follows: 31 CR (Complete Response), 26 PR (Partial Response), 5 SD (Stable Disease), and 0 DP (Disease Progression); 30 CR, 3 PR, 0 SD, 0 DP; and 36 CR, 1 PR, 2 SD, 0 DP. Patient follow-up ranged from 6.8 to 114 mos (median: 38.6 mos). At time of last follow-up, there were 53 alive and 9 dead. Estimated 3-year RFS was 72% (95% "CI": 58.2-81.9%). Estimated 3-year OS was 88.8% (95% CI: 76.6-94.9%). Respective CRRs and ORRs for the primary tumor were 50% (95% CI = 37-63%) and 91.9% (95% CI = 82.2-97.3%); for the groin node 48.4% (95% CI = 35.5-61.4%) and 53.2% (95% CI = 40.1-66%); and for the pelvic node 58.1% (95% CI = 44.8-70.5%) and 59.7% (95% CI = 46.4-71.9%). CRRs and ORRs were not significant prognostic factors for either RFS or OS. <h3>Conclusion</h3> After applying PERCIST to our institutional study cohort, the use of post-treatment PET-CT imaging to predict outcomes for this patient population remains unproven.

Limited-stage small cell lung cancer: Outcomes associated with prophylactic cranial irradiation over a 20-year period at the Princess Margaret Cancer Centre

Background & purposeProphylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution’s 20-year experience with this patient population and associated clinical outcomes. Materials & methodsA retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997–2018) was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005). ResultsA total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p < 0.001). PCI utilization rates did not change between the historic and contemporary treatment era (p = 0.11), whereas magnetic resonance imaging (MRI) use at baseline and follow-up became more prevalent in the contemporary era (p = <0.001). On multivariable analysis, PCI utilization was associated with improved OS (HR 1.88, 95% CI 1.32–2.69) and decreased BFR (HR 4.66, 95% CI 2.58–8.40). Patients who had MRI follow-up had a higher incidence of BFR (HR 0.35, 95% CI 0.18–0.66) in multivariable analyses. ConclusionsFor LS-SCLC patients at our institution, PCI is more frequently utilized in younger patients, and the utilization rate did not change significantly over the past 20 years. PCI was independently associated with improved OS and lower BFR. Omission of PCI in LS-SCLC patients should not be routinely practiced in the absence of further prospective data.

A Pilot Study of a Collaborative Palliative and Oncology Care Intervention for Patients with Head and Neck Cancer.

Background: Palliative care improves symptoms and coping in patients with advanced cancers, but has not been evaluated for patients with curable solid malignancies. Because of the tremendous symptom burden and high rates of psychological distress in head and neck cancer (HNC), we evaluated feasibility and acceptability of a palliative care intervention in patients with HNC receiving curative-intent chemoradiation therapy (CRT). Methods: This was a prospective single-arm study in HNC patients receiving CRT at a single center in the United States. The intervention entailed weekly palliative care visits integrated with oncology care with a focus on symptoms and coping. The primary outcome was feasibility, defined as a >50% enrollment rate with >70% of patients attending at least half of the visits. To assess acceptability, we collected satisfaction ratings post-intervention. We also explored symptom burden, mood, and quality of life (QOL). Results: We enrolled 91% (20/22) of eligible patients. Patients attended 133 of 138 palliative care visits (96%); all 20 attended >85% of visits. Eighteen of 19 (95%) found the intervention "very helpful" and would "definitely recommend" it. QOL and symptom burden worsened from baseline to week 5, but subsequently improved at one-month post-CRT. Overall, patients valued the one-on-one format of the intervention and receipt of additional care. Conclusions: Our palliative care intervention during highly morbid CRT was feasible and acceptable with high enrollment, excellent intervention compliance, and high patient satisfaction. Future randomized studies will further explore the impact on patient-reported outcomes and health care utilization.

A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma

BackgroundPatients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort.MethodsPatients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored.DiscussionCRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC.Trial registration: Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)

Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response

AimsA complete metabolic response (CMR) on early post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a positive prognostic factor for cervical cancer patients treated with definitive chemoradiation, but long-term outcomes of this group of patients are unknown. Patterns of failure and risk subgroups are identified. Materials and methodsPatients who received curative-intent chemoradiation from 1998 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IB1–IVA cervical cancer and had a CMR on post-treatment FDG-PET within 5 months of treatment completion were included. Cox proportional hazards models determined factors associated with locoregional and distant failure. Kaplan–Meier estimates of freedom from any recurrence (FFR) of patient subgroups were compared with Log-rank tests. ResultsThere were 402 patients with a CMR after chemoradiation on FDG-PET. Initial T stage was T1 (38%)/T2 (40%)/T3 (20%)/T4 (2%); initial FDG-avid nodal status was no nodes (50%)/pelvic lymph nodes (40%)/pelvic and para-aortic lymph nodes (10%). After a median follow-up of 6 years, 109 (27%) recurred. The pattern of recurrence was locoregional (27%), distant (61%) or both (12%). No factors were associated with locoregional failure. Distant recurrence was more likely in patients with T3–4 lesions (hazard ratio = 2.4, 95% confidence interval 1.5–3.8) and involvement of pelvic (hazard ratio = 1.6, 95% confidence interval 1.0–2.7) or para-aortic lymph nodes (hazard ratio = 2.7, 95% confidence interval 1.4–5.0) at diagnosis. The 5-year FFR rates for T1–2 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 85, 76 and 62%, respectively (P = 0.04, none versus para-aortic nodes). The 5-year FFR for T3–4 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 68, 56 and 25%, respectively (P = 0.09, none versus para-aortic nodes). ConclusionsT3–4 tumours and para-aortic nodal involvement at diagnosis are poor prognostic factors, even after a CMR following chemoradiation.

Generation of biological hypotheses by functional imaging links tumor hypoxia to radiation induced tissue inflammation/glucose uptake in head and neck cancer

Background and purposePositron emission tomography (PET) is a functional imaging modality which is able to deliver tracer specific biological information, e.g. about glucose uptake, inflammation or hypoxia of tumors. We performed a proof-of-principle study that used different tracers and expanded the analytical scope to non-tumor structures to evaluate tumor-host interactions. Materials and methodsBased on a previously reported prospective imaging study on 50 patients treated with curative intent chemoradiation (CRT) for head and neck squamous cell carcinoma, PET-based hypoxia and normal tissue inflammation measured by repeat 18F-fluoromisonidazole (FMISO) PET and 18F-fluorodesoxyglucose (FDG) PET, respectively, were correlated using the Spearman correlation coefficient R. PET parameters determined before and during CRT (week 1, 2 and 5), were associated with local tumor control and overall survival. ResultsTumor hypoxia at all measured times showed an inverse correlation with mid-treatment FDG-uptake of non-tumor affected oral (sub-)mucosa with R values between −0.35 and −0.6 (all p < 0.05). Mucosal FDG-uptake and mucosal hypoxia correlated positively but weaker (R values between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week 2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4) were significantly associated with worse LC (FMISO TBRpeak: HR = 1.72, p = 0.030; FDG SUVmean: HR = 0.23, p = 0.025) and OS (FMISO TBRpeak: HR = 1.71, p = 0.007; FDG SUVmean: HR = 0.30, p = 0.003). Multivariable models including both parameters showed improved performance, suggesting that these modalities still bear distinct biological information despite their strong inter-correlation. ConclusionWe report first clinical evidence that tumor hypoxia is inversely correlated with increased FDG-uptake during radiation, potentially expressing inflammation. This observation merits further research and may have important implication for future research on tumor hypoxia and radio-immunology. Our study demonstrates that functional imaging can be utilized to assess complex tumor-host interactions and generate novel biological insights in vivo vero.

Vaginal Dilator Utilization in Patients Receiving Curative Radiation for Cancer of the Cervix: A Prospective Study in Botswana

Cervical cancer is the most common malignancy treated with radiation in Botswana and post-treatment dyspareunia and relationship strain is common. To reduce vaginal morbidity following treatment, we introduced a program to offer vaginal dilators in 2017. We sought to assess initial acceptability of vaginal dilators, adherence with use, and barriers to successful use of dilators in a setting with high burden of cervical cancer. Beginning in July 2017, as part of standard clinical care at the sole radiation facility in Botswana, patients with a complete tumor response following curative-intent chemoradiation and brachytherapy, were offered education, a set of vaginal dilators, and lubricant. We analyzed consenting patients in the longitudinal Thabatse Cancer Cohort who received vaginal dilators through December 2019. Patients were reviewed at 6 weeks and thereafter every 3 to 6 months to assess compliance and quality of life. Successful completion of vaginal dilator use was considered as self-reported regular use for 2 years or return to regular sexual activity without dyspareunia. A total of 110 enrolled patients (median Figo stage IIIA) were given dilators. At scheduled 6-week follow-up, 101 (92%) had commenced dilator use. Reasons provided for not starting dilator use were return to regular sexual activity (4), fear of pain (1), fear of bleeding (1), not understanding instructions (1), and no offered reason (2). A successful outcome was observed for 98 (89%)— return to pain-free sexual activity (54, 49%), completed 2 years of use (16, 15%), and continued dilator use (24, 22%). Twelve (11%) women stopped dilator use prior to completion of 2 years. Offered reasons for discontinuing use included: running out of lubricant and pain, bleeding, discomfort with dilator use. Of 58 women returning to sex following treatment for cervical cancer, 50 (86%) were happy with their sex life and 4(7%) reported having pain on sexual intercourse. Reasons offered for not resuming sex were lack/departure of partner, fear of pain, low sexual desire, vaginal dryness, and feeling unwell. During follow up exams, 9 (8%) women provided dilators experienced pain or discomfort on clinical vaginal examination. No moderate or severe adverse effects of dilators were reported. Acceptance of vaginal dilators and self-reported use was high among women completing curative treatment for cervical cancer in Botswana. Further research is needed to optimize patient education and estimate impact of dilator use on function in our population. Retention to dilator use was considerably higher than reported in high-income country contexts and provision of dilators could be especially beneficial in settings like Botswana.