Patient-reported experience with the use of Mepitel Film for prevention of acute radiation dermatitis in breast cancer.

BACKGROUND AND PURPOSE: Mepitel Film (MF) has been demonstrated to reduce the severity of radiation dermatitis (RD) in patients receiving breast cancer radiotherapy (RT). The objective of this study was to characterize patient-reported experience with MF use, including its impact on daily activities and wellbeing. MATERIALS AND METHODS: This single-institution study analyzed anonymized responses to a questionnaire completed by patients who used MF for the prevention of RD during breast cancer RT. RESULTS: Of the 254 patients contacted, 192 patients completed the survey. Most patients disagreed or strongly disagreed that MF limited their ability to perform their daily activities, including household chores (88%, n = 169/191), their ability to work (83%, n = 157/189), or their ability to sleep (85%, n = 163/191). Furthermore, patients agreed or strongly agreed MF was comfortable on their skin (67%, n = 126/189) and protected their skin from rubbing against clothing (86%, n = 161/188). Some patients agreed or strongly agreed that MF affected their ability to shower (31%, n = 50/162), wear bras (28%, n = 51/185), and impacted their level of pruritus (35%, n = 67/189). However, most patients agreed or strongly agreed that their overall experience with MF was positive (92%, n = 173/189) and would recommend MF to a friend undergoing breast cancer RT (88%, n = 166/188). CONCLUSION: MF use is associated with positive patient-reported experience during breast RT with minimal impact on daily activities.

Topical corticosteroids for the prevention of severe radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD. METHODS: A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model. RESULTS: Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale. CONCLUSIONS: The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.

The role of dermocosmetics in the management of cancer-related skin toxicities: international expert consensus.

Skin toxicities are very common in patients undergoing cancer treatment and have been found to occur with all types of cancer therapeutic interventions (cytotoxic chemotherapy, targeted therapies, immunotherapy, and radiotherapy). Further, skin toxicities can lead to interruption or even discontinuation of anticancer treatment in some patients, translating to suboptimal outcomes. Dermocosmetics (or cosmeceuticals)-defined as skincare solutions incorporating dermatologically active ingredients (beyond vehicle effects) that directly improve symptoms of various skin conditions-are increasingly being used in cancer care to prevent and manage skin toxicities. The active ingredients in these products have a measurable biological action in skin; they typically improve skin integrity (barrier function/hydration and other factors) while relieving skin symptoms. The Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC) partnered to select a multidisciplinary group of healthcare professionals involved in the management of patients with cancer and skin toxicities. The group reviewed existing literature and created a summary of recommendations for managing these toxicities through online meetings and communication. In this publication, the group (1) reviews new skin toxicities seen with oncology drugs and (2) evaluates the role of dermocosmetics in improving patient outcomes and minimizing cancer treatment interruptions. We provide general recommendations for initiation and selection of skin care in all oncology patients as well as recommendations for what factors should be considered when using dermocosmetics in specific types of skin toxicities.

Perceptions of healthcare professionals on the use of Mepitel Film for the prevention of acute radiation dermatitis in breast cancer.

INTRODUCTION: Randomized clinical trials support Mepitel Film (MF) as a prophylactic treatment for radiation dermatitis (RD) in patients undergoing breast radiotherapy. Although several studies have canvassed the opinion of patients on using MF, no such studies have been done to investigate the perception of healthcare professionals (HCPs). The objective of this study was therefore to investigate the perceptions of HCPs on MF as a treatment option for RD. METHODS: Anonymized responses to a web-based survey sent to HCPs at a single institution managing patients using MF during breast radiotherapy were analyzed. RESULTS: Of the 28 HCPs contacted, 22 completed the survey, including 6 radiation oncologists (ROs), 11 radiation therapists (RTTs), and 5 nurses. Most HCPs reported MF was better at preventing severe RD than the standard of care and improved radiation-induced skin reactions (n = 20/22, 91%, and n = 19/22, 86%, respectively). MF was recommended for mastectomy patients without reconstruction (n = 15/21, 71%). The majority of HCPs believed that patients' families could be trained to apply and remove MF (n = 19/22, 86%). Many HCPs perceived that implementation of MF would be difficult in terms of maintaining patient flow and wide-scale implementation within their institution (n = 11/22, 50%, and n = 10/22, 46%, respectively). Most HCPs perceived that fewer than 50% of their patients could afford MF if priced at $100 CAD (n = 15/20, 75%). CONCLUSION: These findings provide insights into the possibility of MF to be incorporated into standard practice of care for RD. Although most HCPs were satisfied with MF as a prophylactic treatment for RD, there are concerns about its resource-intensive operationalization and financial accessibility to patients. Future research should focus on ways to improve HCP experience with MF and to improve its implementation into clinical settings as standard of care.

Management trends and outcomes of breast angiosarcoma: Is breast conservation feasible?

We queried the National Cancer Database for nonmetastatic breast angiosarcoma, yielding 808 patients (202 de novo, 606 secondary). The median survival was 53.7 months. Secondary tumors were more likely to undergo mastectomy than de novo lesions (OR = 3.99, P < 0.001). Treatments included lumpectomy (10%), lumpectomy/radiation (3%), mastectomy alone (73%), or mastectomy/radiation (14%), with no difference in survival (P = 0.68). Lumpectomy correlated with positive margin rate (OR 3.29), which was a predictor for death (HR = 2.37, P < 0.01), along with older age, higher comorbidity scores, size >5 cm, and high-grade disease (P < 0.05). While breast angiosarcoma is usually treated with mastectomy, lumpectomy may be feasible for well-selected tumors.

Dosimetric evaluation of multilumen intracavitary balloon applicator rotation in high-dose-rate brachytherapy for breast cancer.

The objective of this work is to evaluate dosimetric impact of multilumen balloon applicator rotation in high-dose-rate (HDR) brachytherapy for breast cancer. Highly asymmetrical dose distribution was generated for patients A and B, depending upon applicator proximity to skin and rib. Both skin and rib spacing was ≤ 0.7 cm for A; only rib spacing was ≤ 0.7 cm for B. Thirty-five rotation scenarios were simulated for each patient by rotating outer lumens every 10° over ± 180° range with respect to central lumen using mathematically calculated rotational matrix. Thirty-five rotated plans were compared with three plans: 1) original multidwell multilumen (MDML) plan, 2) multidwell single-lumen (MDSL) plan, and 3) single-dwell single-lumen (SDSL) plan. For plan comparison, planning target volume for evaluation (PTV_EVAL) coverage (dose to 95% and 90% volume of PTV_EVAL) (D95 and D90), skin and rib maximal dose (Dmax), and normal breast tissue volume receiving 150% (V150) and 200% (V200) of prescribed dose (PD) were evaluated. Dose variation due to device rotation ranged from -5.6% to 0.8% (A) and -6.5% to 0.2% (B) for PTV_EVAL D95; -5.2% to 0.4% (A) and -4.1% to 0.7% (B) for PTV_EVAL D90; -2.0 to 18.4% (A) and -7.8 to 17.5% (B) for skin Dmax; -11.1 to 22.8% (A) and -4.7 to 55.1% (B) of PD for rib Dmax, respectively. Normal breast tissue V150 and V200 variation was < 1.0 cc, except for -0.1 to 2.5cc (B) of V200. Furthermore, 30° device rotation increased rib Dmax over 145% of PD: 152.9% (A) by clockwise 30° rotation and 152.5% (B) by counterclockwise 30° rotation. For a highly asymmetric dose distribution, device rotation can outweigh the potential benefit of improved dose shaping capability afforded by multilumen and make dosimetric data worse than single-lumen plans unless it is properly corrected.

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

Avoiding mastectomy: accelerated partial breast irradiation for breast cancer patients with pacemakers or defibrillators.

INTRODUCTION: The objective of this study was to evaluate the safety, toxicity, and planning concerns involved in accelerated partial breast irradiation (APBI) for patients with breast cancer who have a pacemaker or an automatic implantable cardioverter-defibrillator (AICD) and who desire breast conservation. METHODS: We performed a review of prospectively obtained data for patients with early-stage breast cancer with a pacemaker or AICD treated between April 2007 and July 2010. Patients were treated with either 3D conformal external beam irradiation (3D-CRT) or high-dose rate balloon brachytherapy (HDRBB) as performed in the National Surgical Adjuvant Breast and Nowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol. Device interrogation was performed after the first and last radiation treatment, with comparative cardiac monitoring performed before and after the first three treatments. RESULTS: Eight patients were treated and have a mean follow-up of 6 months. Three patients received HDRBB delivering 34 Gy in 10 fractions. Mean planning target volume for evaluation (PTV_EVAL) coverage was 93.6%. The maximum radiation dose delivered to any device was 1.03 Gy, with a mean pacemaker distance to lumpectomy cavity (DLC) of 9.1 cm. Five patients received 3D-CRT consisting of 38.5 Gy in 10 fractions. The mean 90% PTV_EVAL coverage was 97.3%. Maximum dose delivered to any device was 1.68 Gy at a DLC of 9 cm. Local toxicity did not exceed grade 1, and no adverse device events were noted. CONCLUSIONS: APBI in patients with pacemakers or AICDs who desire breast preservation seems to be a technically safe and reasonable application of targeted radiation therapy.

Objective method to report planner-independent skin/rib maximal dose in balloon-based high dose rate (HDR) brachytherapy for breast cancer.

PURPOSE: An objective method was proposed and compared with a manual selection method to determine planner-independent skin and rib maximal dose in balloon-based high dose rate (HDR) brachytherapy planning. METHODS: The maximal dose to skin and rib was objectively extracted from a dose volume histogram (DVH) of skin and rib volumes. A virtual skin volume was produced by expanding the skin surface in three dimensions (3D) external to the breast with a certain thickness in the planning computed tomography (CT) images. Therefore, the maximal dose to this volume occurs on the skin surface the same with a conventional manual selection method. The rib was also delineated in the planning CT images and its maximal dose was extracted from its DVH. The absolute (Abdiff = [D(max) Man - D (max)DVH]) and relative (Rediff[%] = 100 x ([D(max)Man-D(max)DVH])/D(max)DVH) maximal skin and rib dose differences between the manual selection method (D(max)Man) and the objective method (D(max)DVH) were measured for 50 balloon-based HDR (25 MammoSite and 25 Contura) patients. RESULTS: The average +/- standard deviation of maximal dose difference was 1.67% +/- 1.69% of the prescribed dose (PD). No statistical difference was observed between MammoSite and Contura patients for both Abdiff and Rediff[%] values. However, a statistically significant difference (p value < 0.0001) was observed in maximal rib dose difference compared with maximal skin dose difference for both Abdiff (2.30% +/- 1.71% vs 1.05% +/- 1.43%) and Rediff[%] (2.32% +/- 1.79% vs 1.21% +/- 1.41%). In general, rib has a more irregular contour and it is more proximally located to the balloon for 50 HDR patients. Due to the inverse square law factor, more dose difference was observed in higher dose range (D(max) > 90%) compared with lower dose range (D(max) < 90%): 2.16% +/- 1.93% vs 1.19% +/- 1.25% with p value of 0.0049. However, the Rediff[%] analysis eliminated the inverse square factor and there was no statistically significant difference (p value = 0.8931) between high and low dose ranges. CONCLUSIONS: The objective method using volumetric information of skin and rib can determine the planner-independent maximal dose compared with the manual selection method. However, the difference was < 2% of PD, on average, if appropriate attention is paid to selecting a manual dose point in 3D planning CT images.

Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs.

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue "pocket" for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.

Comparison of single and multiple dwell position methods in MammoSite high dose rate (HDR) brachytherapy planning.

The purpose of this study is to dosimetrically compare two plans generated using single dwell position method (SDPM) and multiple dwell position methods (MDPM) in MammoSite high dose rate (HDR) brachytherapy planning for 19 breast cancer patients. In computed tomography (CT) image-based HDR planning, a surface optimization technique was used in both methods. Following dosimetric parameters were compared for fraction 1 plans: %PTV_EVAL (planning target volume for plan evaluation) coverage, dose homogeneity index (DHI), dose con-formal index (COIN), maximum dose to skin and ipsilateral lung, and breast tissue volume receiving 150% (V150[cc]) and 200% (V200[cc]) of the prescribed dose. In addition, a plan was retrospectively generated for each fraction 2-10 to simulate the clinical situation where the fraction 1 plan was used for fractions 2-10 without modification. In order to create nine derived plans for each method and for each of the 19 patients, the catheter location and contours of target and critical structures were defined on the CT images acquired prior to each fraction 2-10, while using the same dwell-time distribution as used for fraction 1 (original plan). Interfraction dose variations were evaluated for 19 patients by comparing the derived nine plans (each for fractions 2-10) with the original plan (fraction 1) using the same dosimetric parameters used for fraction 1 plan comparison. For the fraction 1 plan comparison, the MDPM resulted in slightly increased %PTV_EVAL coverage, COIN, V150[cc] and V200[cc] values by an average of 1.2%, 0.025, 0.5 cc and 0.7cc, respectively, while slightly decreased DHI, maximum skin and ipsilateral lung dose by an average of 0.003, 3.2 cGy and 5.8 cGy, respectively. For the inter-fraction dose variation comparison, the SDPM resulted in slightly smaller variations in %PTV_EVAL coverage, DHI, maximum skin dose and V150[cc] values by an average of 0.4%, 0.0005, 0.5 cGy and 0.2 cc, respectively, while slightly higher average variations in COIN, maximum ipsilateral lung dose and V200[cc] values by 0.0028, 0.2 cGy and 0.2 cc, respectively. All differences were too small to be clinically significant. Compared to the MDPM, the SDPM combined with a surface optimization technique can generate a clinically comparable fraction 1 treatment plan with a similar interfraction dose variation if a single source is carefully positioned at the center of the balloon catheter.

Evaluation of the interfractional biological effective dose (BED) variation in MammoSite high dose rate brachytherapy.

The objective of this work is to evaluate the interfractional biological effective dose (BED) variation in MammoSite high dose rate (HDR) brachytherapy. Dose distributions of 19 patients who received 34 Gy in 10 fractions were evaluated. A method was employed to account for nonuniform dose distribution in the BED calculation. Furthermore, a range of alpha/beta values was utilized for specific clinical end points: fibrosis, telangiectasia, erythema, desquamation and breast carcinoma. Two scenarios were simulated to calculate the BED value using: i) the same dose distribution of fraction 1 over fractions 2-10 (constant case, CC), and ii) the actual delivered dose distribution for each fraction 1-10 (interfractiondose variation case, IVC). Although the average BED difference (IVC - CC) was < 0.7 Gy for all clinical endpoints, the range of difference for fibrosis and telangiectasia reached -11% to +3% and -9% to +9% for one of the patients, respectively. By disregarding high inhomogeneity in HDR brachytherapy, the conventional BED calculation tends to overestimate the BED for fibrosis by 16% on average, while it underestimates the BED for erythema (7.6%) and desquamation (10.2%). In conclusion, the BED calculation accounting for the nonuniform dose distribution provides a more clinically relevant description of the clinical delivered dose. Though the average BED difference was clinically insignificant, the maximum difference of BED for late effects can differ by a single fractional dose (10%) for a specific patient due to the interfraction dose variation in MammoSite treatment.

ASTRO Radiation Therapy Summary of the ASCO-ASTRO-SSO Guideline on Management of Hereditary Breast Cancer.

PURPOSE: To develop a summary of recommendations regarding locoregional management of patients with breast cancer and germline mutations in breast cancer susceptibility genes based on the American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology Guideline on Management of Hereditary Breast Cancer. METHODS: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an expert panel to develop recommendations based on a systematic review of the literature and a formal consensus process. A total of 58 articles met the eligibility criteria and formed the evidentiary basis for the locoregional therapy recommendations. Additionally, 6 randomized controlled trials of systemic therapy also met eligibility criteria. RESULTS: A joint evidence-based guideline was developed by a multidisciplinary panel, which has been separately published. From this guideline, the radiation-oncologist authors of the panel extracted pertinent surgical and radiation-specific recommendations of findings that are hereby presented. CONCLUSIONS: Patients with newly diagnosed breast cancer and BRCA1/2 mutations may be considered for breast conserving therapy (BCT), expecting similar rates of local control of the index cancer as noncarriers. The significant risk of contralateral breast cancer in these women (especially younger women), coupled with the higher risk of new cancers in the ipsilateral breast, warrant discussion of bilateral mastectomy. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or contralateral breast cancer events from radiation exposure in BRCA1/2 carriers. Patients with mutations in moderate-risk genes should be offered BCT as one choice after appropriate counseling. Radiation therapy should not be withheld in ATM carriers if BCT is planned. For patients with germline TP53 mutations, mastectomy is advised and radiation therapy is contraindicated except for those with a significant risk of locoregional recurrence.

CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands.

Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.

Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes. METHODS: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process. RESULTS: Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria. RECOMMENDATIONS: Patients with newly diagnosed BC and BRCA1/2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.

Managing a small recurrence in the previously irradiated breast. Is there a second chance for breast conservation?

Over the past 30 years, lumpectomy and radiation therapy (breast-conservation therapy, or BCT) has been the preferred treatment for early-stage breast cancer. With accumulating follow-up, we have an ever-expanding pool of patients with history of an irradiated intact breast. Routine use of every-6-month or annual screening in this population has identified an emerging clinical dilemma with respect to managing a small recurrence or a second primary tumor in the treated breast. Most women diagnosed with a second cancer in a previously irradiated breast are advised to undergo mastectomy. More recently, with an improved understanding of the patterns of in-breast failure, and with advances in the delivery of conformal radiation dose there is an opportunity to reevaluate treatment alternatives for managing a small in-breast recurrence. A limited number of publications have reported on patient outcomes after a second lumpectomy and radiation therapy for this clinical scenario. In this report, we review the controversial subject of a second chance at breast conservation for women with a prior history of breast irradiation.

The allegheny general modification of the Harvard Breast Cosmesis Scale for the retreated breast.

The use of brachytherapy--and to a lesser extent, external-beam radiotherapy--in the management of locally recurrent breast cancer following ipsilateral breast tumor recurrence (IBTR) followed by repeat breast-conservation surgery and irradiation is currently an area of intense study. The current cosmetic scoring system is inadequate to score the outcome resulting from retreatment because it does not account for the cosmetic effect of the initial treatment. We propose a modification of the scale for patients who undergo retreatment--the Allegheny General Modification of the Harvard/NSABP/RTOG scoring scale.

Surveillance Mammography After Breast Conservation Therapy: Is Tomosynthesis Worth It?

INTRODUCTION: We investigated the downstream workup and costs associated with digital breast tomosynthesis (DBT) compared with 2-dimensional full field digital mammogram (FFDM) when employed as initial follow-up imaging in breast conservation therapy. METHODS: Between the years 2015 and 2017, 450 consecutive breast conservation therapy patients, ages 32 to 89, with a follow-up DBT (n=162) or FFDM (n=288) were retrospectively reviewed. The primary endpoints were further workup after follow-up mammogram and associated health care costs at 1 year. A single DBT costs an estimated $149 compared with $111 for FFDM, based on Centers for Medicare claims data from the Oncology Care Model. RESULTS: The first posttreatment mammogram was received within 3 (20%), 3 to 6 (32%), or after 6 months (48%) following radiation. Younger patients and those undergoing hypofractionated radiation were more likely to get DBT. There were no differences in stage, receptor status, or mammogram timing between those in the FFDM and DBT groups.The following downstream workup ensued for DBT compared with FFDM imaging: 18% versus 29% short-interval (6-mo) mammogram (odds ratio=1.83, P=0.01), 6% versus 11% breast magnetic resonance imaging (odds ratio=1.90, P=0.08), 4% ultrasound for each, and 3% biopsy for each (1 positive in the FFDM group). Including downstream workup, the estimated cost per patient in the DBT group was $216.14 compared with $237.83 in the FFDM group. Independent predictors for reduced downstream workup per multivariable analysis were the use of DBT and first follow-up mammogram at least 6 months after radiation (P<0.05). DISCUSSION: Excess workup was reduced with DBT compared with FFDM in the posttreatment setting, which translated to an improvement in cost efficiency in this study.

Investigation of interfraction variations of MammoSite balloon applicator in high-dose-rate brachytherapy of partial breast irradiation.

PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.