Neural network dose prediction for cervical brachytherapy: Overcoming data scarcity for applicator-specific models.

BACKGROUND: 3D neural network dose predictions are useful for automating brachytherapy (BT) treatment planning for cervical cancer. Cervical BT can be delivered with numerous applicators, which necessitates developing models that generalize to multiple applicator types. The variability and scarcity of data for any given applicator type poses challenges for deep learning. PURPOSE: The goal of this work was to compare three methods of neural network training-a single model trained on all applicator data, fine-tuning the combined model to each applicator, and individual (IDV) applicator models-to determine the optimal method for dose prediction. METHODS: Models were produced for four applicator types-tandem-and-ovoid (T&O), T&O with 1-7 needles (T&ON), tandem-and-ring (T&R) and T&R with 1-4 needles (T&RN). First, the combined model was trained on 859 treatment plans from 266 cervical cancer patients treated from 2010 onwards. The train/validation/test split was 70%/16%/14%, with approximately 49%/10%/19%/22% T&O/T&ON/T&R/T&RN in each dataset. Inputs included four channels for anatomical masks (high-risk clinical target volume [HRCTV], bladder, rectum, and sigmoid), a mask indicating dwell position locations, and applicator channels for each applicator component. Applicator channels were created by mapping the 3D dose for a single dwell position to each dwell position and summing over each applicator component with uniform dwell time weighting. A 3D Cascade U-Net, which consists of two U-Nets in sequence, and mean squared error loss function were used. The combined model was then fine-tuned to produce four applicator-specific models by freezing the first U-Net and encoding layers of the second and resuming training on applicator-specific data. Finally, four IDV models were trained using only data from each applicator type. Performance of these three model types was compared using the following metrics for the test set: mean error (ME, representing model bias) and mean absolute error (MAE) over all dose voxels and ME of clinical metrics (HRCTV D90% and D2cc of bladder, rectum, and sigmoid), averaged over all patients. A positive ME indicates the clinical dose was higher than predicted. 3D global gamma analysis with the prescription dose as reference value was performed. Dice similarity coefficients (DSC) were computed for each isodose volume. RESULTS: Fine-tuned and combined models showed better performance than IDV applicator training. Fine-tuning resulted in modest improvements in about half the metrics, compared to the combined model, while the remainder were mostly unchanged. Fine-tuned MAE = 3.98%/2.69%/5.36%/3.80% for T&O/T&R/T&ON/T&RN, and ME over all voxels = -0.08%/-0.89%/-0.59%/1.42%. ME D2cc were bladder = -0.77%/1.00%/-0.66%/-1.53%, rectum = 1.11%/-0.22%/-0.29%/-3.37%, sigmoid = -0.47%/-0.06%/-2.37%/-1.40%, and ME D90 = 2.6%/-4.4%/4.8%/0.0%. Gamma pass rates (3%/3 mm) were 86%/91%/83%/89%. Mean DSCs were 0.92%/0.92%/0.88%/0.91% for isodoses ≤ 150% of prescription. CONCLUSIONS: 3D BT dose was accurately predicted for all applicator types, as indicated by the low MAE and MEs, high gamma scores and high DSCs. Training on all treatment data overcomes challenges with data scarcity in each applicator type, resulting in superior performance than can be achieved by training on IDV applicators alone. This could presumably be explained by the fact that the larger, more diverse dataset allows the neural network to learn underlying trends and characteristics in dose that are common to all treatment applicators. Accurate, applicator-specific dose predictions could enable automated, knowledge-based planning for any cervical brachytherapy treatment.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

Forecasting patient-specific dosimetric benefit from daily online adaptive radiotherapy for cervical cancer.

Objective. Adaptive Radiotherapy (ART) is an emerging technique for treating cancer patients which facilitates higher delivery accuracy and has the potential to reduce toxicity. However, ART is also resource-intensive, Requiring extra human and machine time compared to standard treatment methods. In this analysis, we sought to predict the subset of node-negative cervical cancer patients with the greatest benefit from ART, so resources might be properly allocated to the highest-yield patients.Approach. CT images, initial plan data, and on-treatment Cone-Beam CT (CBCT) images for 20 retrospective cervical cancer patients were used to simulate doses from daily non-adaptive and adaptive techniques. We evaluated the coefficient of determination (R2) between dose and volume metrics from initial treatment plans and the dosimetric benefits to theBowelV40Gy,BowelV45Gy,BladderDmean,andRectumDmeanfrom adaptive radiotherapy using reduced 3 mm or 5 mm CTV-to-PTV margins. The LASSO technique was used to identify the most predictive metrics forBowelV40Gy.The three highest performing metrics were used to build multivariate models with leave-one-out validation forBowelV40Gy.Main results. Patients with higher initial bowel doses were correlated with the largest decreases in BowelV40Gyfrom daily adaptation (linear best fit R2= 0.77 for a 3 mm PTV margin and R2= 0.8 for a 5 mm PTV margin). Other metrics had intermediate or no correlation. Selected covariates for the multivariate model were differences in the initialBowelV40GyandBladderDmeanusing standard versus reduced margins and the initial bladder volume. Leave-one-out validation had an R2of 0.66 between predicted and true adaptiveBowelV40Gybenefits for both margins.Significance. The resulting models could be used to prospectively triage cervical cancer patients on or off daily adaptation to optimally manage clinical resources. Additionally, this work presents a critical foundation for predicting benefits from daily adaptation that can be extended to other patient cohorts.

A randomized patient education trial investigating treatment-related distress and satisfaction with the use of an at-home gynecologic brachytherapy educational video.

BACKGROUND: Physician explanation of gynecologic brachytherapy can be overwhelming or induce patient anxiety, and may be time-constrained given clinical limitations. We report the first randomized trial of an educational video intervention in gynecologic brachytherapy on patient-reported outcomes. METHODS: Between February 2020 and January 2022, 80 gynecologic cancer patients prescribed brachytherapy were randomly assigned to either standard informed consent (Arm A) or a supplemental 16 min brachytherapy educational video (https://vimeo.com/403385455/d0716e3cc8) via the internet (Arm B). Primary outcome was treatment-related distress (National Comprehensive Cancer Network (NCCN) distress scale scored 0 (no distress) to 10 (maximum distress)). Secondary outcome was patient satisfaction (summated Likert-scale scored 11-55). Surveys were administered at baseline, after first treatment, and prior to brachytherapy completion. RESULTS: All patients completed the prescribed brachytherapy. In Arm B, 19/40 (48%) patients and 10/40 (25%) patients' family/friends viewed the video. For patients that completed all surveys (Arm A n=29, Arm B n=28), there was no difference between arms in the sociodemographic, clinical, or treatment variables. Distress scores were low at baseline (Arm A median 4, Arm B median 4, p=0.65) and there was no detectable change in distress between arms on surveys 1 and 2 (ß 0.36, p=0.67) or surveys 1 and 3 (ß -1.02, p=0.29) in multivariable analysis. Satisfaction scores were high at baseline (Arm A median 54, Arm B median 54.5, p=0.64) and there was no detectable change in satisfaction between arms on surveys 1 and 2 (ß 0.22, p=0.93) or surveys 1 and 3 (ß 0.63, p=0.85) in multivariable analysis. CONCLUSIONS: Among patients randomized to an educational video tool for gynecologic brachytherapy, approximately 50% of the cohort and 25% of the cohort's family/friends used the video. Overall, patients had low distress scores and high satisfaction scores with no significant differences between the standard and video intervention arms. Further work is needed to understand factors contributing to gynecologic brachytherapy anxiety. TRIAL REGISTRATION NUMBER: NCT04363957.

Outcomes from a 3-fraction high-dose-rate brachytherapy regimen for patients with cervical cancer.

PURPOSE: To estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer. METHODS: 150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28...30 Gy in 4-5 fractions) were reviewed. The primary outcome was 2-year local failure. We compared overall survival (OS), disease-free survival (DFS), hospitalizations, and toxicity. RESULTS: There were 32 patients in the 3F group and 118 in the LF group, with a median follow up of 22 months. The 3F had worse performance status (p = 0.01) but otherwise similar characteristics. The 2-year local failure rate was 3.6% (95% CI 0%, 10.6%) for 3F, and 7.5% (95% CI 2.4%, 12.6%) for LF. The univariable hazard ratio (HR) for local failure for 3F was 0.43 (0.05, 3.43; p = 0.43). Moreover, 2 of 32 (6.3%) 3F patients experienced Grade ...3 toxicity compared to 7 of 118 (5.9%) LF patients (p = 1.0), with no difference in hospitalization within 2 years (p = 0.66) and no treatment-related deaths. CONCLUSIONS: Local control was excellent, with long term survival and toxicity similar between the groups. These findings support consideration of 3F.

Phase 1 Trial of Concurrent Gemcitabine and Cisplatin with Image Guided Intensity Modulated Radiation Therapy for Locoregionally Advanced Cervical Carcinoma.

PURPOSE: The use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC. METHODS AND MATERIALS: We conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center (ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%. RESULTS: Between February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level. CONCLUSIONS: IG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing.

Implementation of peer-review quality rounds for gynecologic brachytherapy in a high-volume academic center.

PURPOSE: While peer review is critical for quality and safety in radiotherapy, there are neither formal guidelines nor format examples for brachytherapy (BT) peer review. We report on a gynecologic BT peer-review method implemented at a high-volume academic center. METHODS AND MATERIALS: We analyzed discussions at bimonthly gynecologic BT peer-review rounds between July and December 2018. Rounds consisted of 2-5 attending physicians with gynecologic BT expertise, 1-2 BT physicists, and trainees. Peer-review targets included clinical case review, contours, implant technique, dose/fractionation, and target/organ-at-risk (OAR) dosimetry. The projected/final target and OAR dosimetry were analyzed. RESULTS: 55 separate implants from 44 patients were reviewed. Implants were mostly reviewed after the first BT fraction (n = 16, 29%) or at another time point during BT (n = 20, 36%). One (2%) implant was presented prospectively. The applicator type and BT technique were reviewed for all implants. Dose/fractionation was evaluated for 46 implants (84%); contours were discussed for 21 (38%). Target and OAR dosimetry were reviewed for 54 (98%) and 28 implants (51%), respectively. Six cases (11%) underwent minor changes to the applicator type to improve target and/or OAR dosimetry. One case (2%) had a major change recommended to the dose/fractionation. CONCLUSIONS: Gynecologic BT peer review may enhance BT quality by allowing for implant optimization and formal review of challenging cases, ultimately improving medical decision-making and team communication. Peer review should be implemented in centers offering gynecologic BT.

Patterns of Recurrence in Node-Positive Cervical Cancer Patients Treated With Contemporary Chemoradiation and Dose Escalation: A Multi-Institutional Study.

PURPOSE: We assessed the effect of elective extended field radiation (EFRT) and nodal dose escalation on locoregional control and survival in patients with node-positive cervical cancer treated with definitive chemoradiation at 2 academic institutions. METHODS AND MATERIALS: Patients with cervical cancer with pelvic and/or paraortic lymph node (PALN) metastases treated with definitive chemoradiation between 2004 and 2011 were retrospectively reviewed. Patterns of failure were recorded. The impact of tumor and treatment on survival or recurrence were evaluated. RESULTS: A total of 78 patients were included. Median follow-up in surviving patients was 34 months. The 3-year overall survival (OS) and disease-free survival (DFS) were 65% and 50%, respectively (all patients), 68% and 52% (pelvic lymph nodes), and 59% and 48% (PALN). OS or DFS in pelvic-only versus PALN-positive patients was not significantly different (log-rank P = .24). Recurrences were distant (n = 22), PALN (n = 6), central pelvis (n = 5), pelvic lymph node (n = 3), and suspended ovary (n = 1). Higher nodal prescribed dose (range, 45-60 Gy) and elective EFRT did not affect DFS or OS (Cox proportional hazards P > .05). There was a trend toward decreased regional recurrence with higher nodal dose (hazard ratio, 0.85 per Gy increase; Cox proportional hazards P = .08). Elective EFRT did not affect PALN failure rate, OS, or DFS (Cox proportional hazards P > .05). CONCLUSIONS: Survival of patients with PALN involvement was similar to those with pelvic-only nodes. Higher nodal dose may improve regional control but did not affect survival. Elective extended-field radiation did not affect outcomes in this cohort. Most failures were distant, emphasizing the potential role of systemic therapy to improve outcomes.

Risk analysis of electronic intraoperative radiation therapy for breast cancer.

PURPOSE: To evaluate the process and improve safety of intraoperative radiation therapy (IORT) for early-stage breast cancers treated with electronic brachytherapy. METHODS AND MATERIALS: A multidisciplinary team conducted a failure mode and effects analysis (FMEA) for IORT breast cancer treatments by first developing a process map. This map was then used to identify failure modes for all steps in the treatment workflow. Risk priority numbers (RPNs) were assigned to each failure mode and were calculated as the product of the failure mode's probability of occurrence (O), severity (S), and lack of detectability (D). Corrective steps were implemented to address failure modes with the highest risk, and a revised process was generated. RESULTS: The steps with the highest risk failure modes were related to source calibration, use of correct plan and dwell times, and the correct site and intent. The introduction of a physician calibration check and an extended time-out checklist reduced the risk of these failure modes. The highest risk steps in the Xoft breast IORT treatment process are associated with source calibration and manual entry of dwell positions for each balloon size and volume combination. High-risk failure modes that could be mitigated with improved hardware and software interlocks were identified. CONCLUSION: High-risk failure modes are identified with FMEA and addressed with corrective steps. This application of FMEA can be used in principle for clinical processes throughout breast cancer care. This analysis demonstrates the importance of well-designed QC policies, procedures, and oversight in a Xoft electronic brachytherapy program for breast cancer IORT.

Treatment outcomes in HPV-negative oropharyngeal cancer: Surgery plus radiotherapy vs. definitive chemoradiotherapy.

We performed a retrospective study to compare clinical outcomes among 51 consecutively presenting patients-38 men and 13 women, aged 46 to 74 years (median: 57)-with locally advanced human papillomavirus (HPV)-negative oropharyngeal cancer who were treated with either primary surgery followed by postoperative radiotherapy (S/RT group; n = 22) or definitive chemoradiotherapy alone (CRT group; n = 29). Within the cohort, 45 patients reported a history of tobacco use, with a median intensity of 40 pack-years. In addition, 39 patients (76%) reported moderate to heavy alcohol use. At baseline, there were no statistically significant differences between the two cohorts in sex, median age, cancer stage, intensity of smoking history, and alcohol use (p > 0.05 for all). Radiation doses ranged from 40 to 70 Gy (median: 70). Follow-up ranged from 2 to 93 months (median: 29). After treatment, we found no difference between the S/RT group and the CRT group in the incidence of locoregional recurrence (36 vs. 24%; p = 0.43) or distant metastases (14 vs. 21%; p = 0.56). Likewise, the difference in 2-year estimates of progression-free survival in the two groups was not significant (66 vs. 62%; p = 0.64), nor was the difference in 2-year overall survival (75 vs. 76%; p = 0.83). We conclude that treatment with either (1) primary surgery followed by postoperative radiotherapy or (2) CRT for locally advanced HPV-negative oropharyngeal cancer results in similar outcomes. In view of the relatively poor prognosis for patients with HPV-negative disease compared with their HPV-positive counterparts, clinical trials to investigate intensifying treatment may be warranted.

Prospective evaluation of patient satisfaction after the use of brachytherapy specific educational materials for cervical cancer.

BACKGROUND: Cervical cancer patients are faced with an enormous amount of medical information in a complex oncology field with sophisticated treatments including brachytherapy. We investigated the use of enhanced vs. standard brachytherapy-specific educational materials on patient-reported satisfaction during the informed consent process for intracavitary high-dose-rate brachytherapy. METHODS AND MATERIALS: A single-institution, prospective, randomized trial was performed to study patient-reported satisfaction with novel educational materials for high-dose-rate brachytherapy in women undergoing definitive radiation for cervical cancer. RESULTS: Fourteen women receiving informed consent with a customized educational booklet were randomized between no further intervention and take-home educational materials. The weighted average for 10 of 11 survey questions was higher in the intervention arm but ranged between 4 (agree) and 5 (strongly agree) for all questions in both arms. The mean weighted patient satisfaction scores ± standard deviations in the control arm and the intervention arms were 54.3 ± 6.4 and 57.5 ± 2.7, respectively (p = 0.26). CONCLUSIONS: Knowledge acquisition is presumed to be part of the coping process for women facing increased stress during a cancer diagnosis. A brachytherapy-specific, visual, patient-educational booklet and take-home materials used to supplement the informed consent process for high-dose-rate brachytherapy resulted in high levels of patient-reported satisfaction among women treated with cervical cancer.

The impact of a vaginal brachytherapy boost to pelvic radiation in stage III endometrial cancer.

PURPOSE: We investigate the use and impact of a vaginal brachytherapy boost (VBB) after pelvic radiotherapy for stage III endometrial adenocarcinoma on vaginal and pelvic control. MATERIAL AND METHODS: One hundred patients treated from 1998-2011 with surgery and adjuvant therapy with or without a VBB were included. Variables examined were grade, stage, lymphovascular space invasion (LVSI), vaginal involvement (VI), cervical stromal involvement (CSI), myometrial invasion (MI), and a VBB. Failure was scored as vaginal, or pelvic. Fisher's exact test assessed association between variables with vaginal and pelvic control. RESULTS: With a median follow up of 43 months, 31% were stage IIIA, 6% stage IIIB, and 63% stage IIIC. Thirty-eight (38%) received pelvic radiotherapy alone, and 62% received adjuvant chemotherapy. Of the 100 patients, 82 were treated with a VBB, 10 were not treated with a VBB, and 8 were not treated with RT. Of the 82 patients who received a VBB, 5 failed in the vagina with vaginal and pelvic control rates of 94% and 92%. The impact of VB reached borderline significance with its impact on pelvic control, 92% vs. 70% (p = 0.056), and did not affect vaginal control, 94% and 90% (p = 0.50). Neither tumor grade, LVSI, CSI, stage, nor LVSI (p > 0.05) statistically significantly impacted vaginal control. CONCLUSIONS: There are no clinical guidelines for the use of a VBB in stage III endometrial cancer. The majority of our patients were treated with a VBB and experienced excellent pelvic and vaginal control. The presence of traditional adverse features did not negatively impact control in our patient cohort. However, the role of a VBB needs further investigation to understand the incremental benefit beyond pelvic RT.

Dose delivered to the lumbosacral plexus from high-dose-rate brachytherapy for cervical cancer.

OBJECTIVE: To calculate dose delivered to the lumbosacral plexus (LSP) with cervical brachytherapy using 3-dimensional imaging, and to compare this with the position of the tandem in the pelvis using bony landmarks. We also report long-term LSP toxicity outcomes. METHODS AND MATERIALS: Treatment planning images from 55 patients treated with tandem and ring brachytherapy from October 2009 through November 2012 were reviewed. The LSP was contoured on planning computed tomographic scans to calculate dose received. Lumbosacral plexus dose was studied as a function of tandem distance from the sacrum and pubic symphysis (STratio) measured on digitally reconstructed radiographs. Patient and implant characteristics were included as covariates on LSP dose. Clinical follow up on LSP toxicity was recorded. RESULTS: Patients were prescribed 550 to 700 cGy using computed tomography-based imaged-guided brachytherapy for 4 to 5 fractions. The maximum dose to 2 cc (D2cc) of LSP ranged from 44 to 287 cGy per implant. The median D2cc was 118 cGy, corresponding to 18% of prescription dose. Patients with an STratio less than 0.33 (closer to the sacrum) and at least 0.33 had median LSP doses of 138 and 98 cGy, respectively. Lumbosacral plexus dose did not change significantly with body mass index, uterus position, or tumor stage. Two patients reported symptoms of peripheral neuropathy, with a median follow-up of 14.7 months. CONCLUSIONS: The mean D2cc per fraction to the LSP is roughly 20% of the prescribed high dose-rate and varies with the position of the tandem from the sacrum. The dose threshold for radiation-induced neuropathy of the LSP remains undefined.

Competing causes of death and medical comorbidities among patients with human papillomavirus-positive vs human papillomavirus-negative oropharyngeal carcinoma and impact on adherence to radiotherapy.

IMPORTANCE: Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. OBJECTIVE: To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. MAIN OUTCOMES AND MEASURES: Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. RESULTS: Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). CONCLUSIONS AND RELEVANCE: Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

Clinical response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer.

PURPOSE: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

The equivalent dose contribution from high-dose-rate brachytherapy to positive pelvic lymph nodes in locally advanced cervical cancer.

PURPOSE: Definitive radiation therapy for locally advanced cervical cancer involves external beam radiation therapy (EBRT) and high-dose-rate (HDR) brachytherapy. There remains controversy and practice pattern variation regarding the optimal radiation dose to metastatic pelvic lymph nodes (LNs). This study investigates the contribution of the pelvic LN dose from HDR brachytherapy. METHODS AND MATERIALS: For 17 patients with 36 positive pelvic LNs, each LN was contoured on a computed tomography (CT) plan for EBRT and on brachytherapy planning CTs using positron emission tomographic images obtained before chemoradiation. The mean delivered dose from each plan was recorded, and an equivalent dose in 2-Gy fractions (EQD2) was calculated. A Student's t test was performed to determine if the mean delivered dose is significantly different from the mean prescribed dose and EQD2. RESULTS: The average prescribed dose from the total EBRT was 54.09 Gy. The average prescribed HDR dose to International Commission on Radiation Units point A was 26.81 Gy. The average doses delivered to the involved LNs from EBRT and brachytherapy were 54.25 and 4.31 Gy, respectively, with the corresponding EQD2 of 53.45 and 4.00 Gy. There was no statistically significant difference (p < 0.05) between the mean delivered and the prescribed doses for EBRT and between the delivered dose and the EQD2 for EBRT and brachytherapy. CONCLUSIONS: Our study shows that the HDR contribution is 7% (4.00 Gy) of the total EQD2 (57.45 Gy). The HDR contribution should be accounted for when prescribing the EBRT boost dose to pelvic LNs for the optimal therapeutic dose.

Interfraction motion of the vaginal apex during postoperative intensity modulated radiation therapy: are we missing the target?

OBJECTIVE: This study aimed to evaluate changes in vaginal cuff position and rectal distention during whole pelvic intensity modulated radiation therapy using daily image guidance for patients with gynecologic malignancies. MATERIALS AND METHODS: We reviewed 145 daily images from 5 patients treated with intensity modulated radiation therapy after total abdominal hysterectomy for endometrial or cervical cancer. A fiducial marker was placed in the vaginal cuff tissue before computed tomographic simulation. The 2008 ASTRO consensus guidelines for delineation of clinical target volumes were used to deliver 45 to 50 Gy to the target structures. Daily megavoltage computed tomographic images were reviewed and changes in position of the fiducial marker as compared to the initial planning scan were recorded in the anterior-posterior (AP), lateral, and superior-inferior dimensions. Changes in rectal distention were also recorded. The position of the fiducial marker relative to the planning target volumes was reviewed on each daily image. RESULTS: The average shifts of the gold seed in the AP, lateral, and superior-inferior dimensions were 7 mm (range, 0-28 mm), 3 mm (range, 0-7 mm), and 2.9 mm (range, 0-12 mm), respectively. Distention of the rectum ranged from 20.5 to 60.1 mm and correlated with movement of the gold seed in the AP dimension (R = 0.53). For 2 patients, the fiducial marker was within 5 mm of the planning target volume margin on 8/40 treatments, or outside the planning target volume on 4/40 treatments. This did not significantly impact total delivered dose to the planning target volume. CONCLUSIONS: Daily image guidance confirms significant interfraction movement of the vaginal cuff tissue, which may exceed suggested guidelines for clinical target volume margins.