Endoscopic assessment of radiological stage IVA cervical cancer: A bivariate meta-analysis supporting an evidence-based staging algorithm proposal.

OBJECTIVE: To optimize the use of confirmatory endoscopic exams (cystoscopy/proctoscopy) in the staging of locally advanced cervical cancer (LACC), the present study evaluates the predictive value of radiological exams (CT and MRI) to detect bladder/rectum invasion. METHODS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42021270329). The inclusion criteria were: a) cervix cancer diagnosis; b) staging CT and/or MRI (index test); c) staging cystoscopy and/or proctoscopy (standard test); and d) numbers of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) provided. A random-effects bivariate meta-analysis of positive predictive value (PPV) and negative predictive value (NPV) was performed with moderator analyses by imaging modality (CT and MRI) and prevalence. RESULTS: Nineteen studies met the inclusion criteria, totaling 3480 and 1641 patients for bladder and rectum analyses, respectively. For bladder invasion (prevalence ranged from 0.9% to 34.5%), the overall PPV was 45% (95% confidence interval, 33%-57%, based on 19 studies). Per subgroup, the PPV was 31% for MRI/prevalence ≤6%, 33% for CT/prevalence ≤6%, and 69% for CT/prevalence >6%. For rectal invasion (prevalence ranged from 0.4% to 20.0%), the overall PPV was 30% (95% confidence interval, 17%-47%, based on 8 studies). Per subgroup, the PPV was 36% for MRI/prevalence ≤1%, 17% for MRI/prevalence >1%, and 38% for CT/prevalence >1%. The overall NPV for bladder invasion and rectal invasion were 98% (95% confidence interval, 97%-99%) and 100% (95% confidence interval, 99%-100%), respectively. Considering prevalence and radiological modality, the point estimate of NPV varied from 95% to 100% for bladder invasion and from 99% to 100% for rectum invasion. CONCLUSIONS: Due to low PPV (<50%) of radiological staging, endoscopic exams may be necessary to correctly assess radiological stage IVA LACC. However, they are not necessary after negative radiological exam (NPV ≥95%).

Non-invasive stereotactic ablative boost in patients with locally advanced cervical cancer.

INTRODUCTION: The current literature is insufficient to guide care for patients with cervical cancer ineligible for brachytherapy. Stereotactic ablative radiotherapy boost is a clinical necessity for these patients, but highly debated among radiation oncologists. OBJECTIVE: To report toxicity and survival outcomes in a large cohort of patients with locally advanced cervical cancer treated with a non-invasive stereotactic ablative radiotherapy boost instead of brachytherapy METHODS: Patients with locally advanced cervical cancer were entered, between January 2008 and December 2018, who were recommended definitive intent external boost after pelvic radiotherapy to 45-50.4 Gy concurrent with weekly cisplatin and simultaneous/sequential nodal boost up to 55-66 Gy. Simulation CT was facilitated using radio-opaque fiducials, empty rectum, dedicated bladder filling, and whole body vaculoplastic immobilization. Kaplan-Meier survival estimates were used to report local/regional recurrences, distant metastases, cancer-specific survival, and overall survival. RESULTS: A total of 25 patients were analyzed. Median follow-up was 25 months (range 6-54). Patients received stereotactic ablative radiotherapy due to refusal of brachytherapy (9/25, 36%), medical co-morbidities limiting implantation (9/25, 36%), or technical infeasibility (7/25, 28%). Typical fractionation was 24-30 Gy in 4-5 fractions (24/25, 96%). The most common long-term toxicity was grade 1-2 vaginal dryness, discomfort, stenosis, and/or dyspareunia (4/25, 16%). One patient had new post-treatment grade 4 fistula in an area of previous tumor erosion (1/25, 4%). Overall survival, cancer specific survival, loco-regional control, and distant control were 95.5%, 100%, 95.5%, and 89.1%, respectively, at 2 years. CONCLUSION: Further study of stereotactic ablative radiotherapy boost for cervical cancer is needed; a brachytherapy-similar approach portends clinical success with 95.5% overall survival and loco-regional control at 2 years.

Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Factors Associated With Radiation Treatment Compliance for Women With Cervical Cancer in a Safety Net Health System.

OBJECTIVE: The aim of the study was to determine whether patient characteristics are associated with radiation treatment noncompliance. METHODS/MATERIALS: We retrospectively studied 244 patients with cervical cancer treated with chemoradiation between May 2006 and August 2015 at a safety net health center. Compliance with treatment was defined as missing less than 2 days of scheduled radiation. RESULTS: Treatment records revealed a compliance rate of 50.8% in this population. Factors associated with noncompliance were younger age (hazard ratio [HR], 1.037; P = 0.004), presence of psychiatric diagnosis (HR, 0.581; P = 0.044), and having insurance (HR, 0.484; P = 0.022). Noncompliance was associated with a decrease in disease-free survival (HR, 0.555; P = 0.042) but was not associated with overall survival. International Federation of Gynecology and Obstetrics stage was associated with detriment in overall survival on multivariate analysis (HR, 2.034; P = 0.001). CONCLUSIONS: Younger patients, those with psychiatric illness, and those with insurance define a group that is more likely to be noncompliant with treatment and hence may require up-front intervention to improve outcomes.

Metformin use and improved response to therapy in esophageal adenocarcinoma.

BACKGROUND: We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin. MATERIAL AND METHODS: Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. RESULTS: The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥ 1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05). CONCLUSION: Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.

Effect of Quality of Life on Radiation Adherence for Patients With Cervical Cancer in an Urban Safety Net Health System.

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear. METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, then weekly during RT and at follow-up. Patient information was abstracted from the medical record. Radiation nonadherence was defined as missing ≥2 days of external beam RT. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 total and subscale scores were compared between adherent and nonadherent patients. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Ninety-three patients were enrolled, completing 522 surveys. Median age at diagnosis was 46 years (interquartile range, 40-51); 76% of patients were Hispanic, and 12% were Black. Only 30% of patients were nonadherent with RT. A psychiatric comorbidity (P = .012) and symptomatic presentation (P = .027) were associated with decreased adherence. Baseline total QoL was higher in treatment-adherent than in nonadherent patients (median, 124.86; range, 48-160; 108.9, 46-150; P = .01). Higher baseline functional and physical subscale scores were associated with adherence (P < .05). Change from baseline to lowest score during treatment in the emotional subscale was also associated with patient adherence (P < .05). In multivariable analysis, higher baseline physical score, baseline total score, and change in emotional subscale score were associated with adherence (P < .05). CONCLUSIONS: Poor QoL during chemoradiation for cervical cancer is associated with missed treatments. Physician assessment of a patient's well-being while they are undergoing RT is of utmost importance to improve adherence to treatment.

Prevalence of pathogenic germline variants in adult-type diffuse glioma.

Background: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma. Methods: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected. Results: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH, and CHEK2 were most common (3/15, 20% each). BRCA1 variants occurred in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Prior cancer diagnosis was found in 5/15 patients (33%). Second-hit somatic variants were seen in 3/15 patients (20%) in NF1, MUTYH, and MSH2. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. 14/15 (93%) of patients discovered their pathogenic variant as a result of their paired glioma sequencing. Conclusions: These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further studies that can determine the role of variants in gliomagenesis and confirm the occurrence and types of pathogenic germline variants in patients with IDH wild type compared to IDH mutant tumors are necessary.

Predictors of follow-up non-compliance after definitive radiotherapy for locally advanced cervical cancer at a community cancer center.

Introduction: Non-compliance to post-treatment cancer surveillance can lead to late detection of recurrence. This study aims to identify patients at high risk for loss of follow-up after radiotherapy for locally advanced cervical cancer. Methods: Consecutive patients with locally advanced cervical cancer treated with definitive chemoradiotherapy (2013-2020) at a community cancer center were retrospectively reviewed. The main outcome was overall follow-up compliance rate over time. Additionally, specialist-specific follow-up times, reasons for discontinuation and predictors of loss of follow-up events were evaluated. Results: The median age of the 154 patients included was 46.5 years (range: 26-84). The 6-month, 1-, 3-, and 5-year overall loss of follow-up rates were: 5.3%, 15.3%, 33.6%, and 48.2%, respectively. After a median overall follow-up time of 21.0 months, the median specialist-specific surveillance times were 17 months and 6 months with gynecologic and radiation oncologists, respectively (p < 0.01). Overall, the most common reasons for loss of follow-up were financial (21.7%) and relocation to another city (28.3%). By specialty, the most common reasons were relocation of care (56.5%, gynecologic oncologist) and disease progression (31.3%, radiation oncologist). In the multivariable analysis, older age (continuous, OR: 0.96; p < 0.01) and Hispanic ethnicity (OR: 0.39; p < 0.01) were protective against loss of follow-up, while increased number of gestations (continuous, OR: 1.23, p = 0.01) and living farther from the cancer center (continuous, OR: 1.002; p = 0.03) increased the chance of loss of follow-up. Conclusion: Younger, non-Hispanic, multiparous women that live far from the community cancer center have an increased chance of follow-up discontinuity, which are attributed to financial reasons in more than 20% of the cases.

Paracervical blocks facilitate timely brachytherapy amidst COVID-19.

PURPOSE: The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: This technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment. RESULTS: 18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D2cc for rectum and bladder were 64.8 (58.6-70.2) Gy and 84.1 (70.9-89.4) Gy, respectively. Median (IQR) CTV high-risk D90 was 88.0 (85.6-89.8) Gy. CONCLUSIONS: In a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.

Video-assisted thoracoscopic lobectomy is associated with greater recurrence-free survival than stereotactic body radiotherapy for clinical stage I lung cancer.

OBJECTIVE: Stereotactic body radiotherapy is the standard treatment for medically inoperable early-stage non-small cell lung cancer. Recent data suggest that in operable patients, stereotactic body radiotherapy produces outcomes comparable to those of surgical resection. In veterans with early non-small cell lung cancer, we compared the outcomes of stereotactic body radiotherapy and video-assisted thoracoscopic lobectomy. METHODS: We retrospectively reviewed data from 183 patients (94.0% male) with clinical stage I non-small cell lung cancer who underwent stereotactic body radiotherapy (n = 56) or video-assisted thoracoscopic lobectomy (n = 127) from 2009 to 2014. Propensity matching was used to produce more comparable groups. Primary end points were tumor control and overall, recurrence-free, and lung-cancer-specific survival, as estimated by Kaplan-Meier actuarial analysis. Multivariable analysis was used to identify independent predictors. RESULTS: In the overall cohort, the patients who received stereotactic body radiotherapy were older than the patients who received video-assisted thoracoscopic lobectomy (median age, 79.5 vs 64 years) and had more comorbidities. In the 37 propensity-matched pairs, the 3-year actuarial tumor control rate was 54.3% after stereotactic body radiotherapy and 90.6% after video-assisted thoracoscopic lobectomy (P = .0038). Actuarial lung cancer-specific 3-year survival was 78.1% (stereotactic body radiotherapy) versus 93.6% (video-assisted thoracoscopic lobectomy) (P = .055). One-year overall, 3-year overall, and 3-year recurrence-free survivals were 89.2%, 52.9%, and 38.5% after stereotactic body radiotherapy and 94.6%, 85.7%, and 82.8% after video-assisted thoracoscopic lobectomy (P < .005 for all), respectively. In multivariable analysis, stereotactic body radiotherapy independently predicted recurrence and poorer survival. CONCLUSIONS: In veteran patients with early-stage non-small cell lung cancer, video-assisted thoracoscopic lobectomy resulted in better disease control and survival than stereotactic body radiotherapy. Although prior reports suggest that stereotactic body radiotherapy is a suitable alternative to surgery in early-stage lung cancer, a prospective randomized trial is needed. Nevertheless, stereotactic body radiotherapy remains a suitable option for medically inoperable patients.

Proton therapy radiation pneumonitis local dose-response in esophagus cancer patients.

PURPOSE: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. MATERIALS/METHODS: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. RESULTS: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p=0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. CONCLUSIONS: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope.