D.P. Horowitz

Patterns of care and treatment outcomes for elderly women with cervical cancer

Cervical cancer is common in the elderly. The authors examined the patterns of care, treatment, and outcomes of elderly women with cervical cancer.

Secretory carcinoma of the breast: Results from the survival, epidemiology and end results database

BACKGROUND Secretory carcinoma of the breast is a rare breast cancer that is associated with incidence at a young age and an indolent course. The role for breast conservation and adjuvant radiation is unknown. METHODS The SEER database was reviewed and 83 patients were identified with secretory carcinoma of the breast between the years 1983 and 2007. Baseline characteristics were compared with χ(2) or Fishers exact test. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. Analyses were performed using PASW Statistics, version 18. RESULTS Median follow-up was 70 months. Median patient age was 53 years (range 11-86 years). 29 patients (34.9%) had involved regional lymph nodes. 39 patients (47.0%) underwent lumpectomy and 44 patients (53.0%) underwent mastectomy. 35 patients (42.2%) received radiation. Patients receiving radiation were more likely to have undergone lumpectomy, and the use of radiation increased over time. 5-year OS was 87.2%; 10-year OS was 76.5%. 5-year CSS was 94.4%; 10-year CSS was 91.4%. Among the lumpectomy patients, 25 patients (64.1%) received radiation. For lumpectomy patients, those who did not receive radiation had a 5-year OS of 92.9% and 10-year OS of 72.2% while patients who did receive radiation had a 5-year OS of 95.5% and 10-year OS of 85.9%. Only 1 patient treated with lumpectomy only died of cancer (92.9% CSS) and no patients treated with lumpectomy and radiation died of cancer (100% CSS). CONCLUSIONS Secretory carcinoma of the breast commonly occurs at a later age than previously recognized, and is associated with good long-term survival.

The Role of Definitive Radiotherapy in Craniopharyngioma: A Seer Analysis

Objective: Assess patterns of care in the management of craniopharyngioma, especially with respect to the use of radiation therapy (RT) alone (which has been understudied to date) as compared with gross total resection (GTR) and subtotal resection (STR) with adjuvant RT. Materials and Methods: The epidemiology, treatment modalities, and outcomes of patients with craniopharyngioma were studied using the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2012. Survival was compared between treatment groups using Kaplan-Meier analysis and log-rank tests. Results: In total, 1218 patients with craniopharyngioma were identified, with equal distribution across sex. There were bimodal incidence peaks, one 20 years old or below, and the other between 40 and 65 years. The majority of pediatric tumors with known histology were adamantinomatous type, which did not influence outcomes when adjusting for age (P=0.392). Overall survival/cause-specific death for patients that underwent RT, STR+RT, and GTR were not statistically different (P>0.05). There was improved survival between several modalities: RT only versus STR only (P=0.024), RT only versus observation (P=0.006), STR+RT versus observation (P=0.046), and GTR versus observation (P=0.046). Patients above 65 years old were more likely to undergo observation (P=0.002), with highest proportions of surgery (54%)/RT (21%) in the pediatric population. Multivariable analysis demonstrated that though age was associated with overall survival (P<0.001), treatment modality (RT/GTR/STR+RT) was not (P=0.119). Conclusions: Although management of craniopharyngioma remains somewhat controversial, there were no observed differences in outcomes between definitive RT, GTR, and STR+RT. Although these data are hypothesis-generating, additional data are needed to validate these findings.

De-escalation of radiation dose for human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma: A case report and preclinical and clinical literature review

Traditionally, head and neck squamous cell carcinoma (HNSCC) has been considered to be a relatively homogeneous disease. However, recent data have demonstrated that human papillomavirus (HPV)-positive and HPV-negative disease are two different clinical entities associated with different outcomes. Preclinical and clinical studies have reported a divergence in treatment strategies as well as prognostic outcomes for HNSCCs that are HPV-positive versus HPV-negative. The present study describes the case of a 52-year-old man who presented with stage IVB cT2N3M0 right tonsillar HPV-positive squamous cell carcinoma. Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), followed by chemoradiation therapy with carboplatin and 70 Gray (Gy) radiation in daily fractions was recommended. The patient completed the TPF and carboplatin treatment; however, he was unable to tolerate the radiation course, receiving a final dose of 46 Gy. A 60-day follow-up right neck salvage dissection was subsequently performed. Despite having received a partial radiation treatment of 46 Gy, the patient had no pathological evidence of disease at 60 days post radiation treatment. Repeat positron emission tomography-computed tomography at 32 months after the right neck dissection revealed no evidence of disease. The present study also discusses the current preclinical in vitro and in vivo targets for HPV-positive HNSCC and the obstacles presented in advancing clinical treatment modalities. Previous preclinical models investigating radiation sensitivity have yielded mixed results. Thus, it is important to understand and establish representative preclinical models for studying HPV and HNSCC to improve clinical research and therapeutic development. This review may guide future understanding of the role of HPV in HNSCC.

Evaluation of Partial Breast Reirradiation with Intraoperative Radiotherapy after Prior Thoracic Radiation: A Single-Institution Report of Outcomes and Toxicity

Introduction Mastectomy is the current standard of care for ipsilateral breast tumor recurrences after prior whole breast irradiation (WBI). We report our single-institution experience with breast-conserving surgery (BCS) followed by intraoperative radiotherapy (IORT) as an alternative to salvage mastectomy for new or recurrent breast cancers that develop in the setting of prior thoracic radiation. Methods We performed an IRB-approved retrospective review of patients treated with breast IORT between September 2013 and November 2016. We identified 12 patients who declined salvage mastectomy for their breast cancer after prior thoracic radiation. IORT was delivered using the Intrabeam™ device (Carl Zeiss, Germany). A dose of 20 Gy was prescribed to the lumpectomy cavity surface using 50 kV X-rays. We graded both acute and late treatment-related breast toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Local control, mastectomy-free survival, distant metastasis, and overall survival were determined. Results Our study included nine patients who developed a new or recurrent ipsilateral breast cancer after prior WBI for early-stage breast cancer, two patients with primary breast cancer after mantle-field radiation for Hodgkin’s lymphoma, and one patient with a synchronous stage III non-small cell lung cancer treated with definitive radiation to the ipsilateral lung and mediastinum. The median time from prior radiation to presentation was 18 years (range: 2 months to 46 years). All patients successfully underwent partial breast reirradiation with IORT and were able to preserve their breast. At a median follow-up of 14 months (4–25 months), there were no local or distant recurrences. There was a single non-cancer-related death. In the acute setting, we observed grade 1 toxicity in 58% (n = 7), grade 2 toxicity in 17% (n = 2), and no grade 3 or higher toxicity. In the late setting, at least 3 months after IORT, we observed grade 1 hyperpigmentation and/or fibrosis in 50% (n = 6), symptomatic seroma requiring drainage in 33% (n = 4). A single patient developed an abscess requiring hospitalization and intravenous antibiotic therapy. Conclusion BCS with IORT is a feasible salvage option for patients who present with localized breast cancer after prior thoracic radiation treatment. Continued follow-up of these patients is warranted given the incidence of delayed toxicity.

Radiation Therapy Deviations in Trial of Locally Advanced Pancreatic Cancer

Radiation Therapy Deviations in Trial of Locally Advanced Prostate Cancer To the Editor The LAP07 trial found no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone for patients with locally advanced pancreatic cancer.1 Radiation therapy quality assessment was included in the study because this has been demonstrated to significantly affect outcomes in pancreatic cancer.2 The authors found that only 32% of patients received radiation per protocol with violations “mainly due to dose distribution heterogeneities.” In their results, they commented that “deviations from the planned schedule did not significantly influence overall survival,” but later in the discussion that “deviations from the planned protocol ... did not affect significantly the overall survival.” Radiation quality assessment includes many other factors (target volume delineation, coverage limitations, etc) in addition to adherence to the radiation schedule. Was adherence to these factors studied for its influence on outcome? If not, we encourage the authors to report on those patients who were treated with radiation “per protocol” against those with anything “less than per protocol,” as was done in the study by Abrams and colleagues.2 The radiation target volumes used in the study differ significantly from those required in the ongoing NRG Oncology Cooperative Group study of the treatment of locally advanced pancreatic adenocarcinoma, Radiation Therapy Oncology Group (RTOG) 1201 (ClinicalTrials.gov NCT01921751). The RTOG 1201 protocol specifies targeting of the tumor and involved lymph nodes rather than treating multiple echelons of uninvolved lymph nodes with large radiation fields. Results from the ongoing study may help clarify whether different approaches to radiation target delineation will affect outcomes.

Comparing preoperative imaging modalities in patient selection for breast intraoperative radiotherapy: MAY et al.

This study evaluated the relative accuracy of mammography, ultrasound, and magnetic resonance imaging (MRI) in predicting the tumor size of early stage breast tumors in preoperative selection of patients for intraoperative radiotherapy (IORT).

Breast conservation for male breast cancer: Case report of intraoperative radiation

Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62‐year‐old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow‐up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.

Koebner phenomenon: Consideration when choosing fractionation for breast irradiation

A 62-year-old woman with a remote medical history of psoriasis initially presented with a palpable right breast mass. She underwent right breast ultrasound that revealed a hypoechoic mass at 10:30, 6 cm from the nipple, that measured 1.7 × 2.1 × 2.1 cm. Biopsy of the mass revealed invasive ductal carcinoma. Subsequent breast magnetic resonance imaging scans confirmed the right breast cancer, but also revealed a suspicious left breast region at 1:00. Biopsy of the left breast mass revealed a radial scar. The patient was evaluated by both breast and plastic surgery physicians and subsequently underwent right partial mastectomy and sentinel lymph node biopsy and excisional biopsy for the radial scar followed by bilateral oncoplastic breast reduction. Final pathology showed right breast multifocal invasive ductal carcinoma, grade 3, with no involved sentinel nodes, and left breast ductal carcinoma in situ. The patient’s postoperative course was complicated by bilateral seromas requiring drainage as well as bilateral breast cellulitis treated with antibiotics. She was evaluated by the radiation oncology department, and the decision was made to delay starting radiation to allow adequate wound healing. In the interim, she was started on Anastrazole 1 mg. The patient was assessed weekly, and eventually radiation was begun on the right breast, with the left side delayed to allow for further healing. The patient was treated in the prone position with hypofractionated whole breast radiation therapy (WBRT) of 42.56 Gy in 16 fractions with a 10 Gy boost to the right breast starting November 21. She completed treatment on December 21 without treatment breaks. During the second week of treatment, using daily Hydrophor and topical hydrocortisone as needed, the patient developed grade 1 erythema and pruritus of the right breast. After her leftsided seroma drainage resolved, she started adjuvant hypofractionated WBRT of 42.56 Gy in 16 fractions to the left breast on January 5, which she completed on January 27 without treatment breaks. During the second week of treatment, the patient developed grade 1 erythema of the left breast. Her right breast erythema improved with mild hyperpigmentation. The patient was seen for routine follow-up on March 1 approximately 1 month after completing her left breast radiation course. The patient noted that the erythema in her left breast was resolving (Fig 1a); however, over the course of the following few days, she noted a new rash on her right breast (Fig 2a) in the distribution of her radiation field (Fig 2b), along with similar rashes in her right inguinal region (Fig 1b) and her left wrist. The patient’s psoriasis had been inactive for more than 5 years. She was seen by her dermatologist, who suspected Koebner phenomenon. The patient underwent biopsy of the right inguinal rash; Conflicts of interest: None. * Corresponding author. Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032. E-mail address: dph2119@cumc.columbia.edu (D.P. Horowitz). 1 C.-C.W. and S.W. contributed equally to this work. Advances in Radiation Oncology (2018) 3, 108–110

Management of Esophageal Squamous Cell Carcinoma with Definitive Chemoradiotherapy in a Patient with Scleroderma: Case Report and Review of the Literature

Scleroderma is a disease characterized by fibrosis of the skin and internal organs, and is associated with changes in microvasculature. The association of scleroderma with malignancy has been debated, with early cohort studies showing no increase in the incidence of cancer among patients with scleroderma [1, 2]. Subsequent studies showed an increased incidence of lung cancer, breast cancer, esophageal cancer, oropharyngeal cancer, non-melanoma skin cancer, and lymphoproliferative malignancies in patients with scleroderma [2–9]. Both adenocarcinoma and squamous cell carcinoma of the esophagus have been described as occurring with increased incidence in patients with scleroderma [10]. Patients with scleroderma are thought to have increased incidence of gastric reflux, development of Barrett’s esophagus, and subsequent development of esophageal adenocarcinoma, though this has not yet been validated in a prospective manner [11–13]. Overall, patients with scleroderma have a standardized incidence ratio of 15.9–33 for the development of esophageal cancer compared to the general population [5, 14]. Current National Comprehensive Cancer Network guidelines for locoregional esophageal cancer indicate that for patients with tumors extending into or through the submucosa, medically fit patients with operable tumors should undergo multidisciplinary evaluation [15]. For tumors extending into but not through the submucosa, primary esophagectomy is recommended. For tumors extending into or through the muscularis, or those tumors with locoregional lymph node involvement, multimodality therapy is recommended, with Consent Written informed consent was obtained from the patient for publication of the case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.