PURPOSE:Literature supporting the efficacy of complementary and integrative medicine (CIM) alongside radiotherapy is fragmented with varying outcomes and levels of evidence. This review summarizes the available evidence on CIM used with radiotherapy in order to inform clinicians.METHODS:A systematic literature review identified studies on the use of CIM during radiotherapy. Inclusion required the following criteria: the study was interventional, CIM therapy was for human patients with cancer, and CIM therapy was administered concurrently with radiotherapy. Data points of interest were collected from included studies. A subset was identified as high-quality using the Jadad scale. Fisher's exact test was used to assess the association between study results, outcome measured, and type of CIM.RESULTS:Overall, 163 articles met inclusion. Of these, 68 (41.7%) were considered high-quality trials. Articles published per year increased over time (p < 0.01). Frequently identified therapies were biologically based therapies (47.9%), mind-body therapies (23.3%), and alternative medical systems (13.5%). Within the subset of high-quality trials, 60.0% of studies reported a favorable change with CIM while 40.0% reported no change. No studies reported an unfavorable change. Commonly assessed outcome types were patient-reported (41.1%) and provider-reported (21.5%). Rate of favorable change did not differ based on type of CIM (p = 0.90) or outcome measured (p = 0.24).CONCLUSIONS:Concurrent CIM may reduce radiotherapy-induced toxicities and improve quality of life, suggesting that physicians should discuss CIM with patients receiving radiotherapy. This review provides a broad overview of investigations on CIM use during radiotherapy and can inform how radiation oncologists advise their patients about CIM.

The purpose of this study was to compare skin dose in postmastectomy patients with tissue expanders who have been treated with either a 3D printed bolus or a superflab bolus. We retrospectively collected data from 43 postmastectomy women with tissue expanders who were treated with radiation from 2013 to 2019. Forty of these women were treated with a daily 5-mm superflab bolus, and three women were treated with a daily 5-mm 3D printed bolus. Within the first three days of starting radiation therapy, we measured the surface dose in vivo at five anatomical locations under the 5-mm bolus on the chest wall. For the patients treated with a 3D printed bolus, a cone-beam CT was obtained 2-3 times a week during treatment. On each cone beam CT, a line was drawn in the treatment field at a point that would give a maximum distance for a line perpendicular to the plane of both the bolus and chest wall. This distance was recorded as the maximum air gap. For superflab vs. 3D printed bolus patients, a two-sample t-test assuming unequal variances was used to compare the mean percentages of prescribed dose at the median, central, lateral, superior, and inferior portion of the chest wall. These were 94.8% vs 100.9% (p-value <.001), 103.0% vs 113.1% (p-value = .007), 97.5% vs 105.1% (p-value = .177) 101.9% vs 109.2% (p-value = .032), 106.7% vs 113.3% (p-value<.001), respectively. To quantify the mean percentage of the prescribed dose to the whole chest wall, the values from all the optically stimulated luminescence dosimeters were averaged. For the superflab patients and 3D printed bolus patients, the mean percentages of prescribed dose were 100.8% vs. 108.3% (p-value = .001), respectively. See table 1. In the patients with a 3D printed bolus, the mean maximum airgap was 1.3 cm, with a standard deviation of .3 cm. This study demonstrates that in postmastectomy patients with expanders, a 3D printed bolus is associated with higher mean percentages of prescribed dose for the median, central, superior, and inferior portions of the chest wall compared to superflab bolus.Abstract 2092; TableChest wall locationPercentage of Prescribed DoseSuperflab3D-Printed Bolusp-valueMedian94.8%100.9%<.001Central103.0%113.1%= .007Lateral97.5%105.1%= .177Superior101.9%109.2%= .032Inferior106.7%113.3%<.001Average100.8108.3%= .001 Open table in a new tab

Objective: Cervical cancer patients considered to be at high risk for paraaortic lymphatic involvement may receive extended-field chemoradiation (EF-CRT), with inclusion of the paraaortic region. Increased radiation to bone marrow (BM) may heighten hematologic toxicity (HT) and have an impact on timely delivery of chemotherapy and radiation. Factors (including radiation planning metrics) associated with HT in this setting have not been well-studied.

Hypofractionated (HF) radiotherapy (RT) is now recommended for the majority of women undergoing breast conserving surgery (BCS). Oncoplastic reconstruction (OR) combines BCS with plastic surgery techniques to allow for oncologic resection while preserving cosmesis. Cosmesis and toxicity for OR with conventionally fractionated (CF) RT is well established. While HFRT is now standard of care, there are limited data reporting cosmesis for women undergoing HFRT after OR. Given OR is a cosmetic procedure, this study aimed to demonstrate acceptable late toxicity and post-treatment cosmesis with HFRT after BCS and OP. Women with > 3 months of follow-up after treatment with BCS, OR and HFRT between 2010 and 2018 were identified. Surgery was performed either as a single or staged procedure with immediate or delayed reconstruction. All women received 42.56 Gy to the whole breast using field-in-field technique. A lumpectomy cavity boost was performed at the discretion of the treating physician. Demographic, disease and treatment characteristics, and toxicity outcomes were recorded. For a subset of patients, pre and post-operative photos were maintained. Cosmesis at the time of most recent follow-up was independently rated by two plastic surgeons and two radiation oncologists (excellent, good, fair, poor). Chi-squared, Mann-Whitney U, and logistic regression were used to assess association between patient/treatment related factors and toxicity. 38 women were identified with a median follow-up of 12 months from completion of HFRT. Median age was 61.5 (61% white, 30% black, and 9% mixed /other). 55% underwent a single procedure with immediate reconstruction. 61% had local tissue rearrangement alone, 20% had mastopexy and reduction, and 24% had flap rearrangement. 16% of women received a lumpectomy cavity boost. Due to inability to accurately delineate the post-surgical tumor bed, the lumpectomy cavity was only contoured in 66% of women. Surgical toxicities were reported in 12% women prior to HFRT. Late cosmesis related toxicities were found in 52% women (table 1) of which the majority (58%) were skin toxicity (all RTOG grade 1). There was no significant association between age, race, BMI, comorbidities, receptor status, chemotherapy status, HFRT treatment position, boost, V105, or max point dose and late cosmesis. Of the cohort with longitudinal photos, cosmesis was rated as excellent in 42%, good in 46%, and fair in 12%. There were no locoregional failures. OR with HFRT has good toxicity profiles and favorable physician rated cosmetic outcomes. It offers an acceptable alternative to CFRT. Further investigation of patient reported cosmesis and prospective evaluation of OR and HFRT is warranted.Abstract 2113; Table 1Late Toxicityn (%)Pain3 (7)Edema4 (12)Fibrosis2 (5)Dimpling0 (0)Nipple retraction2 (5)Volume loss1 (2)Skin changes11 (29) Open table in a new tab

HPV subtypes correlate with prognostic features and outcomes in cervix cancer patients treated with primary surgery or radiotherapy. We report the incidence of HPV subtypes and outcomes in cervical cancer patients treated with definitive chemoradiotherapy. A single institutional retrospective review was performed on 51 patients from 2/2010-7/2017 treated with definitive chemoradiation, including lymph node (LN) boost when indicated. PCR was performed on patient biopsy samples to determine HPV subtyping. Data on age at diagnosis, race, prior cancer history, smoking status, FIGO stage, tumor grade, distant metastases at diagnosis, pelvic and para-aortic node involvement at diagnosis, tumor size, time to first recurrence, overall survival and follow-up time were collected. Univariate and multivariable analyses were performed based on HPV subtype. Kaplan-Meier method and the log-rank tests were used to compare overall survival and time to first recurrence. HPV was detected in 84% of biopsy samples, with HPV 16 in 51% (26), HPV 18 in 14% (7), HPV 33 in 8% (4), HPV 45 in 10% (5), and HPV 52 in 2% (1) of tumors. HPV grouping was defined as group 1(HPV 18), group 2 (HPV 16), group 3 (HPV 33,45, and 52) and group 4 (no HPV). Based on results from univariate analysis, prior history of cancer, positive pelvic lymph nodes (pLNs) at diagnosis and smoking status were analyzed on multivariate analysis. When comparing group 1 to group 3, there was a statistically significant difference in pLNs found at the time of diagnosis with positive pLNs being found in 86% of group 1 patients and only 40% of group 2 patients (p=0.045). There was also a trend towards a higher rate of pLN incidence in group 1 when compared to group 4, with the latter having positive pLNs 62% of the time. Additionally, there was a trend for group 1 patients to have had a higher rate of other cancers prior to diagnosis with 14% of group 1 patients having a prior non-skin cancer diagnosis compared to 11% of group 2 patients (p=0.156), 0% of group 3 patients (p=0.081), and 0% of group 4 patients (p=0.148). Overall survival and time to first recurrence between the various groups were not statistically significant. Our study demonstrates that HPV subtype correlates with having positive pLNs at the time of diagnosis. HPV 18 subtype had the highest rate of pLN involvement. This may support use of appropriate imaging studies for staging and treatment intensification strategies when treating patients with an HPV 18 subtype.

A key component of the three-dimensional conformal (3DCRT) and intensity-modulated radiation therapy (IMRT) treatment planning process is contouring organs at risk (OARs) to accurately calculate dose to these structures. Diagnostic images are frequently fused to the simulation CT scan to help delineate target volumes and OARs. Unlike target volumes, contouring of OARs and image fusion both are often done by a dosimetrist or physicist. This study hypothesized that the accuracy of OAR contours and image fusions are not routinely reviewed by treating physicians, which could negatively impact treatment plan quality and safety. An anonymous, internet-based survey of medical physicists and dosimetrists was created in REDCap and distributed via the MEDPHYS and MEDDOS listserv groups 2/4-2/22/19. Participants were asked to characterize standard practices for completion and review of OAR contouring, target volume contouring, and image fusion at their institution, their personal training in these areas, and level of comfort performing these tasks. Percentages are reported as percent [95% confidence interval]. Of 273 individuals who responded to the survey (response rate 4%), 76% were medical physicists or medical physics residents and 24% were dosimetrists. Practice setting was 67% community-based, 26% academic institution, and 7% government-owned facility. 67% practice in the United States, 15% Europe, 9% Asia, and 9% other. Dosimetrists and/or medical physicists enter all of the OAR volumes in 63% [57, 69] of responses and perform all of the image fusion in 89% [85, 92] of responses, while 74% [69, 79] responded that only physicians enter target volumes. Only 19% [13, 25] reported a formal process by which OAR volumes are reviewed by physicians at their practice. 21% [15, 28] of the individuals at institutions without a formal review process stated that physicians “rarely or never” review OAR volumes, while 0% [0, 10] of individuals at institutions with a formal review process reported this (p<0.01). Presence of a formal review process was associated with significantly higher perceived thoroughness of review of OAR volumes (p<0.01). Although physician review of image fusion was reported to be more regular and thorough than review of OAR volumes, presence of a formal review process was also associated with higher rates of image fusion review (p<0.01). Despite the critical role of OAR contouring and image fusion in 3DCRT and IMRT treatment planning, rates of physician review of these steps in the treatment planning process, as reported by dosimetrists and medical physicists, are not always optimal. Radiotherapy clinics should consider implementation of a formal OAR and image fusion review process to ensure the quality and safety of treatment plans.

Comparison of outcomes and shifts in stage using the 2018 FIGO cervical cancer staging in patients with known paraaortic lymph node status treated with definitive chemoradiation (CRT) has not been described. Our goal is to report these shifts and outcomes. A single institutional retrospective review was performed on 141 patients with IRB approval who received definitive CRT from 2000-2018. Patient data, including PET/CT or CT for work-up, were used to determine shifts with restaging from the FIGO 2009 to the FIGO 2018 system. Survival was then analyzed using log-rank tests to compare overall survival. Of 141 cervical patients staged per FIGO 2009, 15% (21) and 30.4% (43) were stage II and III, respectively (Table 1). Re-analysis with FIGO 2018 system resulted in higher stage in all subgroups except IAI, IA2, IVA, and IVB disease. Upstaging occurred in the majority of patients: 8 (73%) of the stage IB1 patients, (37% to IB2, 9% to IB3, and 27% to IIIC1), 18 (100%) of stage IB2 patients, (67% to IB3, 28% to IIIC1, and 5% to IIIC2), 3 (27%) of stage IIA1 patients, (9% to IIIC1 and 18% to IVB), 5 (50%) of stage IIA2 patients, (40% to IIIC1 and 10% to IIIC2), 19 (54%) of stage IIB patients (20% to IIIC1, 23% to IIIC2, and 11% to IVB), 3 (75%) of the stage IIIA patients (75% to IIIC1), 28 (72%) of the stage IIIB patients, (38% to IIIC1, 18% to IIIC2, 3% to IVA, and 13% to IVB). Survival analysis was performed to compare FIGO 2009 and 2018 staging without any statistical significance seen between the two groups for stage I (p=0.79), stage IIA (p=0.88), stage IIB (p=0.42), stage IIIA/IIIB (p=0.86), and stage IV (p=0.16). A trend toward significance when comparing survival for the FIGO 2009 IIIA/IIIB and FIGO 2018 IIIC2 stage was noted with stage IIIC2 patients having a worse median survival (33 months) compared to stage IIIB/IIIA patients (66 months), p=0.059. Migration to higher stage subgroups occurred in the majority of patients with use of the FIGO 2018 staging system. Survival outcomes for stages I, II, IIIA, IIIB, and IV correlate with the previous 2009 system. Para-aortic node involvement on imaging (FIGO stage IIIC2) correlated with worse survival that trended towards significance when compared to stage FIGO IIIA/IIIB disease, validating the utility of separating these two groups.Abstract 2766; Table 1Staging shifts based on FIGO 2009 vs. FIGO 2018 stagingFIGO 2009Total Number of Patients (141)FIGO 2018Stage 1A1, 1A22 (1%), 2 (1%)Same stageStage 1B1, 1B2, 1B311 (8%), 18 (13%), NAUpstaged 8 (73%), 18 (100%), NAStage IIA1, IIA211 (8%), 10 (7%)Upstaged 3 (27%), 5 (50%)Stage IIB35 (25%)Upstaged 19/35 (54%) 7/35 (20%) - Stage IIIC1 8/35 (23%) - Stage IIIC2 4/35 (11%) - Stage IVBStage IIIA4 (3%)Upstaged 3/4 (75%) 3/4 (75%)- Stage IIIC1Stage IIIB39(27%)Upstaged 28/39 (72%) 15/39 (38%) -Stage IIIC1 7/39 (18%) - Stage IIIC2 1/39 (3%) - Stage IVA 5/39 (13%)- Stage IVBStage IIIC1 and IIIC2NAStage IVA and IVB5/141 (4%) and 4/141 (3%)Same stageOverall141Same stage 57/141 (40%) Upstaged 84/141 (60%) Open table in a new tab

The anxiety burden of patients with breast cancer is well documented and is associated with worse outcomes. Mindfulness-based stress reduction is a validated therapy that has shown efficacy for these patients. Prior work has tested professional meditation courses in the setting of survivorship. This study pilots a brief daily electronically-guided meditation intervention delivered in the radiotherapy clinic concurrent with treatment. The objectives were to determine whether there were barriers to completing the intervention and whether patients who did so would demonstrate changes in anxiety over the course of their radiation treatment.

Effective communication with patients decreases anxiety, pain, and psychological distress. National guidelines recommend readability of patient education materials be at or below a 6th grade level. However, radiation oncology materials average a 10th grade level. The Communicating the External Beam Radiation Experience (CEBRE) discussion guide, a novel graphic narrative educational tool, was developed. A pilot study evaluated perceived benefits of CEBRE. CEBRE was designed as a collaboration between physicians and designers. Designers conducted structured interviews of patients, family members, and radiation oncology clinic staff. Interviews were coded for themes to uncover stakeholder-based insights, leading to design principles driving the design of CEBRE. The CEBRE discussion guide comprehensively covers the external beam radiation care path from consultation through follow-up. A “My information” section includes patient-specific information to facilitate a tailored discussion. Readability was measured using the Flesch-Kincaid (FK) test. A pilot perceived benefits study utilized a survey to determine usability and effect on anxiety in patients. Modified versions of the Systems Usability Score (SUS) and Spielberger State-Trait Anxiety Inventory short form (STAI) along with questions unique to CEBRE were included. Patients receiving treatment or in active follow-up and practicing radiation oncologists were asked to review CEBRE and complete separate patient and physician perceived-benefit surveys. Likert-type scores are reported as median [interquartile range]. The CEBRE guide scores a 5.4 FK grade level, meeting national guidelines. 34 patients and 12 radiation oncologists completed perceived benefits surveys. Patients completed a high school/GED (18%), a 2-year degree or some college (50%), or at least 4 years of college (32%). Patient and physician responses were concordant. On a scale of 1-5 for the modified SUS and 1-4 for the modified STAI (“strongly disagree” to “strongly agree”) the median modified SUS is 4 [4-5] for each cohort and modified STAI scores were 3 [3-4] and 3 [3-3.5] for patients and providers, respectively. Both cohorts “agree” CEBRE is usable and would decrease patient anxiety. Compared to a text only pamphlet, the graphic narrative component of CEBRE was rated as “quite” helpful 4 [4-5] by both cohorts. Patient qualitative responses revealed that presentation of the CEBRE guide by a care provider would make them feel even more comfortable. Providers reported the CEBRE guide would be “quite helpful” 4 [4-5] compared to a text-only pamphlet, that with CEBRE “patients will understand more” 4 [4-5], and providers are “extremely likely” 5 [3-5] to use CEBRE at initial consultation. The CEBRE discussion guide is a patient accessible and practical education tool that warrants further investigation in the radiation oncology clinic.

In patients with locally advanced cervix cancer, extended field radiotherapy (EFRT) is often utilized to provide coverage of the para-aortic nodes. This results in a large portion of the bone marrow (BM) being included within the radiation field. We evaluated hematologic toxicity in cervix cancer patients treated with EFRT concurrent chemoradiotherapy during an institutional transition from IMRT to VMAT and to compare feasibility in achieving BM dose constraint metrics with comparison plans generated for a subset of patients. From 2007-2017, 34 patients with Stage IB1-IVA cervix cancer treated with EFRT (45 Gy/1.8 Gy) with a simultaneously-integrated boost (SIB) to gross nodal disease (55 Gy /2.2 Gy) and concurrent chemotherapy (C) using IMRT or VMAT were identified . With institutional review board approval, each patient’s chart was reviewed and evaluated for hematologic toxicity, C dose reduction, and treatment duration. For 7 selected patients, IMRT and VMAT plans were generated to directly compare feasibility of meeting BM constraints. EFRT clinical target volumes (CTVs) were contoured to the renal veins with a 7 mm uniform expansion to create a planning target volume (PTV). The BM was defined as the bones of the pelvis, sacrum and lumbar spine to the top of the PTV. Using these target volumes, an IMRT plan with 7 angles and a 2-arc VMAT plan were created for each of the 7 patients. The target planning goal was to cover the PTV by ≥ 95% of the prescribed dose. Dose constraints included V10 < 90%, V20 < 75% and V40 < 37% for BM; V35 <33%, V50 < 10cc and max <56 Gy for bowel; V40 < 50% and max < 49.5 Gy for bladder; V35 < 10% for femora; and V18 < 30% for kidney. Chi-square, student’s t-test and two-sided Wilcoxon’s test were used for statistical analysis (p<0.05 was considered to be significant). Of the 34 patients identified, 25 were treated using IMRT and 9 using VMAT. All but two patients received SIB. All BM planning parameters (V10, V20, V40) were achieved in 4 of 7 VMAT plans, 6 of 11 IMRT plans; 2 of 9 VMAT and 13 of 25 IMRT plans were planned without BM constraints. A significant difference was seen in acute Grade 3-4 hematologic toxicity (IMRT 60.0% vs VMAT 33.3%, p=0.001), but not in C dose reduction (29.4% vs 11.1%, p=0.38), or treatment length (54 days vs 55 days, p=0.62). In plans generated for dosimetric comparison with equivalent PTV45 and PTV55 coverage, VMAT plans had significantly decreased BM V20 (73.6% vs 77.5%, p=0.02) and V40 (23.7% vs 28.1%, p=0.03). No significant differences were seen in the BM V10. In this analysis, we found that VMAT techniques provided plans with improved BM sparing (V20 and V40 parameters). In treated patients, those planned with VMAT had lower rates of severe (grade 3-4) hematologic toxicity compared to those treated with IMRT.

Historically, PMB was standard practice in locally advanced cervical cancers to provide sufficient dose to involved parametria. Modern 3D imaging, as well as high-dose rate (HDR) and interstitial (IS) brachytherapy techniques have improved the delineation and coverage of a high-risk clinical target volume (HRCTV) while allowing for higher dose delivery. PMB has become increasingly controversial in the era of IGBT. Due to the lack of data on safety of omitting PMB, patterns of failure with and without use of PMB were explored. Women with locally advanced (FIGO Stage IIB-IVA or with PM invasion identified on imaging) cervical cancer diagnosed between 2001-2016 were identified. All patients received external beam radiotherapy (EBRT) and brachytherapy boost (BT) using either low-dose rate (LDR) or HDR sources (prescribed to point A and HRCTV, respectively). HRCTV was contoured using MRI guidance (either diagnostic or with apparatus in place). PMB was delivered to achieve a cumulative dose of 56-60 Gy to the lateral parametria. Demographic, treatment era (pre and post 2009), pre-treatment imaging modality, FIGO stage, lymph node status, PMB, BT modality (IS vs. tandem & ovoid, T&O), dose rate, and patterns of failure were collected. Cramer’s V and chi-squared tests were used to assess strength of association between variables. The log-rank test was used for univariate analysis (UVA) and a Cox proportional hazards model was created for multivariable analysis (MVA). Overall survival (OS) was estimated using Kaplan-Meier analysis A total of 71 women were identified with median follow up of 25 months. 36 women received PMB. Median doses were as follows: EBRT 45 Gy, PMB 4.5 Gy, HDR BT 29.5 Gy, and LDR 40 Gy. 37 women received HDR and 34 received LDR BT. Six patients who did not receive PMB had PM involvement only on imaging. PMB patients were less likely to have received diagnostic MRI, PET, or IS and more likely to receive LDR. The use of PET, dose rate, and treatment era were highly correlated with one another (Cramer’s V 0.7-0.9, p<0.001). 2-year OS was 74%. On UVA, treatment year, use of PET, use of MRI, and dose rate were associated with OS (all p<0.05). In an MVA including PMB, age, race, nodal status, FIGO stage, and PET, para-aortic nodal involvement (HR= 4.33, 95% CI 1.01-10.7, p=0.049) and use of PET (HR=0.22, 95% CI 0.1-0.7, p=0.007) were associated with OS. PMB was associated with higher crude rates of local (22% vs. 6%, p=0.049), locoregional (30% vs. 6%, p=0.01), and distant failure (28% vs. 9%, p=0.04). In this retrospective study, the omission of PMB did not compromise local control or impact OS in the setting of IGBT. At our institution, PMB treatment has gradually been eliminated in cervical cancer treatment. Adaptive IGBT provides accurate identification and dose shaping of HRCTV previously unachievable in the 2D era, allowing for targeting of gross parametrial involvement.

There have been numerous bolus regimens published for post-mastectomy chest wall radiation therapy. These regimens vary in the thickness of the bolus and the schedule of its application, and may lead to errors in application or increased skin toxicity. We present the dosimetric and toxicity outcomes for women treated with daily two millimeter (mm) chest wall bolus applied to the skin for the entirety of treatment. We performed a single institution analysis on a subset of women treated with post-mastectomy radiation who were enrolled in a prospective database. We analyzed the dosimetry and toxicity of the initial 25 patients treated with daily 2 mm chest wall bolus when the technique was instituted at our institution in 2013. For treatment planning, an ideal 2 mm chest wall bolus was created in the treatment planning system. For treatment, 2 mm bolus was placed daily for all treatment fields, and optically stimulated luminescent dosimeters (OSLD) were placed in all treatment fields on the first day of treatment. Twenty-five women were treated with daily 2 mm chest wall bolus. The median age was 55 years. Sixty and forty percent of patients received radiation for left and right sided disease, respectively. OSLD readings were obtained for 52% of women. The median dose to the skin under the 2 mm bolus was 185 cGy [range 161-220 cGy], which was 103% (range 89.4% -122.2%) of the prescription dose. Grade 1, 2, and 3 skin toxicities were observed in 33.3%, 58.3%, and 8.3% of patients respectively. For women receiving post-mastectomy chest wall radiation therapy, daily 2 mm chest wall bolus, for all treatment fields and the entire duration of each daily treatment, demonstrates adequate dose build-up with acceptable acute skin toxicity.

Purpose/Objective(s)Intensity-modulated radiation therapy (IMRT) has become increasingly integrated into the treatment of breast cancer. The objective of this study is to identify predictors for the use of IMRT in a population-based cohort of young women undergoing adjuvant radiation therapy (RT) following breast conserving surgery.Materials/MethodsThe nation-wide MarketScan Commercial and Medicare-Supplemental insurance claims database was used to select 5,572 women younger than 65 years of age with non-metastatic breast cancer treated with BCS followed by adjuvant RT. All women had a minimum of 3 years follow-up after diagnosis. Univariate analysis was performed to identify clinical and demographic characteristics that predicted for the type of adjuvant therapy, and included age, Charlson comorbidity score (CCS), median income of county of residence, diagnosis year, geographic region, and surgeon and radiation oncologist density. Multivariable analysis (MVA) was performed using logistic regression to determine the impact of the covariates on the probability of receiving IMRT.ResultsSeven hundred thirty-one (13%) patients received IMRT, while 4,841 were not treated with IMRT. There was no difference in the median age (53 for both, p = 0.74) or endocrine therapy use (60% vs 63%, p = 0.149) between the two groups. Patients receiving IMRT were from areas with lower median income ($50,213 vs $52,391; p < 0.001), and more likely to have CCS ≥1 (19% vs 14%; p < 0.001). There was no difference in IMRT use between women in metropolitan vs non-metropolitan areas (13% vs 14%; p = 0.451). Women in the South census region of the country were most likely to receive IMRT (18%; p < 0.001). Women receiving IMRT were more likely to receive image-guided radiation therapy (8% vs 2%; p < 0.001). IMRT use increased over the time period from 2003-2010 from 5% to 32% (p < 0.001). There was no difference in subsequent mastectomy (4% vs 3%; p = 0.550) or metastasis (11% vs 9%; p = 0.162) MVA revealed that higher than median surgeon density (Odds Ratio [OR]: 1.44, 95% Confidence Interval [CI]: 1.09-1.90; p = 0.012), lower than median radiation oncologist density (OR: 1.77, CI: 1.33-2.35; p < 0.001), CCS ≥1 (OR: 1.41, CI: 1.15-1.73; p = 0.001), diagnosis after 2006 (OR: 1.23, CI: 1.05-1.44; p < 0.010), and South census region (OR: 1.99, CI: 1.68-2.37; p < 0.001) predicted increased IMRT use. Younger age (p = 0.874), median income (0.467), and metropolitan area (0.375) were not associated with IMRT use.ConclusionsSeveral clinical and demographic factors predict for the use of IMRT in young, commercially-insured, women following BCS. The use of IMRT in this cohort of women has increased over the last decade. Purpose/Objective(s)Intensity-modulated radiation therapy (IMRT) has become increasingly integrated into the treatment of breast cancer. The objective of this study is to identify predictors for the use of IMRT in a population-based cohort of young women undergoing adjuvant radiation therapy (RT) following breast conserving surgery. Intensity-modulated radiation therapy (IMRT) has become increasingly integrated into the treatment of breast cancer. The objective of this study is to identify predictors for the use of IMRT in a population-based cohort of young women undergoing adjuvant radiation therapy (RT) following breast conserving surgery. Materials/MethodsThe nation-wide MarketScan Commercial and Medicare-Supplemental insurance claims database was used to select 5,572 women younger than 65 years of age with non-metastatic breast cancer treated with BCS followed by adjuvant RT. All women had a minimum of 3 years follow-up after diagnosis. Univariate analysis was performed to identify clinical and demographic characteristics that predicted for the type of adjuvant therapy, and included age, Charlson comorbidity score (CCS), median income of county of residence, diagnosis year, geographic region, and surgeon and radiation oncologist density. Multivariable analysis (MVA) was performed using logistic regression to determine the impact of the covariates on the probability of receiving IMRT. The nation-wide MarketScan Commercial and Medicare-Supplemental insurance claims database was used to select 5,572 women younger than 65 years of age with non-metastatic breast cancer treated with BCS followed by adjuvant RT. All women had a minimum of 3 years follow-up after diagnosis. Univariate analysis was performed to identify clinical and demographic characteristics that predicted for the type of adjuvant therapy, and included age, Charlson comorbidity score (CCS), median income of county of residence, diagnosis year, geographic region, and surgeon and radiation oncologist density. Multivariable analysis (MVA) was performed using logistic regression to determine the impact of the covariates on the probability of receiving IMRT. ResultsSeven hundred thirty-one (13%) patients received IMRT, while 4,841 were not treated with IMRT. There was no difference in the median age (53 for both, p = 0.74) or endocrine therapy use (60% vs 63%, p = 0.149) between the two groups. Patients receiving IMRT were from areas with lower median income ($50,213 vs $52,391; p < 0.001), and more likely to have CCS ≥1 (19% vs 14%; p < 0.001). There was no difference in IMRT use between women in metropolitan vs non-metropolitan areas (13% vs 14%; p = 0.451). Women in the South census region of the country were most likely to receive IMRT (18%; p < 0.001). Women receiving IMRT were more likely to receive image-guided radiation therapy (8% vs 2%; p < 0.001). IMRT use increased over the time period from 2003-2010 from 5% to 32% (p < 0.001). There was no difference in subsequent mastectomy (4% vs 3%; p = 0.550) or metastasis (11% vs 9%; p = 0.162) MVA revealed that higher than median surgeon density (Odds Ratio [OR]: 1.44, 95% Confidence Interval [CI]: 1.09-1.90; p = 0.012), lower than median radiation oncologist density (OR: 1.77, CI: 1.33-2.35; p < 0.001), CCS ≥1 (OR: 1.41, CI: 1.15-1.73; p = 0.001), diagnosis after 2006 (OR: 1.23, CI: 1.05-1.44; p < 0.010), and South census region (OR: 1.99, CI: 1.68-2.37; p < 0.001) predicted increased IMRT use. Younger age (p = 0.874), median income (0.467), and metropolitan area (0.375) were not associated with IMRT use. Seven hundred thirty-one (13%) patients received IMRT, while 4,841 were not treated with IMRT. There was no difference in the median age (53 for both, p = 0.74) or endocrine therapy use (60% vs 63%, p = 0.149) between the two groups. Patients receiving IMRT were from areas with lower median income ($50,213 vs $52,391; p < 0.001), and more likely to have CCS ≥1 (19% vs 14%; p < 0.001). There was no difference in IMRT use between women in metropolitan vs non-metropolitan areas (13% vs 14%; p = 0.451). Women in the South census region of the country were most likely to receive IMRT (18%; p < 0.001). Women receiving IMRT were more likely to receive image-guided radiation therapy (8% vs 2%; p < 0.001). IMRT use increased over the time period from 2003-2010 from 5% to 32% (p < 0.001). There was no difference in subsequent mastectomy (4% vs 3%; p = 0.550) or metastasis (11% vs 9%; p = 0.162) MVA revealed that higher than median surgeon density (Odds Ratio [OR]: 1.44, 95% Confidence Interval [CI]: 1.09-1.90; p = 0.012), lower than median radiation oncologist density (OR: 1.77, CI: 1.33-2.35; p < 0.001), CCS ≥1 (OR: 1.41, CI: 1.15-1.73; p = 0.001), diagnosis after 2006 (OR: 1.23, CI: 1.05-1.44; p < 0.010), and South census region (OR: 1.99, CI: 1.68-2.37; p < 0.001) predicted increased IMRT use. Younger age (p = 0.874), median income (0.467), and metropolitan area (0.375) were not associated with IMRT use. ConclusionsSeveral clinical and demographic factors predict for the use of IMRT in young, commercially-insured, women following BCS. The use of IMRT in this cohort of women has increased over the last decade. Several clinical and demographic factors predict for the use of IMRT in young, commercially-insured, women following BCS. The use of IMRT in this cohort of women has increased over the last decade.

Peripheral blood lymphocytes (PBLs) of patients with cervical intraepithelial neoplasia (CIN), cervical carcinoma, or early breast carcinoma were tested for the expression of T cell receptor zeta chain (TCR zeta) and CD16 zeta chain and production of interferon-gamma (IFN gamma) and interleukin (IL) 10. We found that in all patients with CIN and invasive cervical carcinoma, PBLs showed a reduced TCR zeta and CD16 zeta expression and a significant down-regulation in IFN gamma production (a T helper 1 cytokine) after anti-CD3 stimulation. However, the IL 10 secretion (a T helper 2 cytokine) was not diminished after anti-CD3 stimulation. This indicates that only T helper 1 cells are affected by the down-regulation of the TCR zeta chain expression. We also analyzed PBLs of 12 patients with early breast carcinoma. In these patients, we found TCR zeta and CD16 zeta expression down-regulation in 2 of 12 patients. Six of 12 patients had an enhanced TCR zeta expression. The enhanced TCR zeta expression correlated with a reduced IFN gamma expression after anti-CD3 stimulation. These data show that in general PBLs of early breast carcinoma patients, unlike those of cervical carcinoma patients, do not show a decreased TCR zeta expression. However, a functional impairment of T cells was observed in the subgroup of early breast carcinoma patients with a high nuclear grade of their tumor.

Two human squamous cell cervical carcinoma cell lines, C-33A (HTB 31) and MS751 (HTB 34), were exposed to either paclitaxel alone or paclitaxel for 24 hr followed by graded doses of Cs-137 radiation. Each was then analyzed for both clonogenic survival and alterations to cell cycle progression. No radiosensitization or affect on the cell cycle was seen using 1 × 10−9Mpaclitaxel. Each line was equally sensitive to the drug with approximately 50% cell lethality seen after 1 × 10−8Mof paclitaxel. This concentration of paclitaxel also produced substantial G2M arrest, seen immediately after drug exposure and lasting up to 2 days. Gamma radiation delivered during the time of G2M arrest showed only a small degree of radiosensitization by paclitaxel for the relatively radioresistant MS751 line at 4 Gy (SF4= 16.0 ± 3.2% → 5.7 ± 1.1%,P= 0.049) but no sensitization using radiation doses of conventional fraction size [sensitizer enhancement ratios 1.1 (0.80–1.40) and 1.3 (0.95–1.65) for the C-33A and MS751 cell lines, respectively]. It is concluded that paclitaxel produces only a modest radiosensitization effect, indicating that this compound will have limited benefit as a radiosensitizer for the treatment of cervical cancer.

DNA analysis by flow cytometry has been reported to be a useful prognostic technique for a variety of malignant tumors. The goal of this study was to examine DNA ploidy status and proliferation index as potential predictors of recurrence and survival for patients with squamous cell vulvar carcinomas. The DNA ploidy, percentage of cells in the S-phase of the cell cycle, stage, and histologic grade were analyzed in 42 patients. Flow cytometry was performed on archival paraffin-embedded tissue. The histologic specimens were reviewed by a single pathologist. Thirty-four tumors (81%) were diploid and eight (19%) demonstrated an aneuploid peak. The percentage of cells in the S-phase (proliferation index) was calculated for all patients. The 5-year survival rate was 68% for diploid tumors and was 75% for aneuploid tumors. The difference between these rates was not statistically significant (P < or = 0.65). S-phase fraction was also not a useful predictor for recurrence or overall survival. FIGO stage and histologic grade were accurate predictors for both recurrence and 5-year survival. Multiple predictor analysis using stage, grade, ploidy status, and proliferation index did not identify any subgroup which would predict recurrence better than FIGO stage and grade. DNA ploidy and S-phase fraction analysis do not appear to be clinically useful prognostic factors for vulvar squamous cell carcinomas.