Ethan B. Ludmir

Human papillomavirus tumor infection in esophageal squamous cell carcinoma

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.

Total neoadjuvant therapy for rectal cancer: An emerging option

The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results. Shifting systemic therapy delivery to the neoadjuvant setting has the promise to improve compliance rates, reduce toxicity, and decrease distant relapse rates. Recently, multiple prospective trials have reported on the use of total neoadjuvant therapy (TNT) for patients with LARC, incorporating both ChT and CRT in the neoadjuvant setting. Here, the authors review the promising results from those trials. Because the studies have largely focused on pathologic outcomes (primarily pathologic complete response rates), ongoing phase 2 and 3 trials are now underway assessing the long‐term disease‐related outcomes with TNT. In addition to improving survival, TNT has the potential to increase the pool of patients with LARC who are eligible for organ preservation, which is also being evaluated. Cancer 2017;123:1497–1506.

Mixed Adenoneuroendocrine Carcinoma, Amphicrine Type, of the Small Bowel

OBJECTIVES Amphicrine-type mixed adenoneuroendocrine carcinomas are exceedingly rare lesions of the gastrointestinal tract, comprising tumor cells simultaneously demonstrating both neuroendocrine and exocrine features. To date, only 14 cases of amphicrine carcinoma have been reported; here we report the first definitive case of amphicrine carcinoma in the small bowel. METHODS A 72-year-old woman who sought treatment for nonspecific abdominal complaints was found to have a duodenojejunal junction tumor and underwent radical surgical resection. RESULTS Morphologically, the tumor consisted of areas of moderately differentiated adenocarcinoma intermingled with areas characteristic of neuroendocrine tumor. The entire tumor showed strong, diffuse immunoreactivity for synaptophysin. Coexpression of exocrine and neuroendocrine features by neoplastic cells indicates bivalent differentiation, and therefore the tumor was classified as an amphicrine carcinoma of the small bowel. CONCLUSIONS Demonstration of amphicrine carcinoma in the small bowel carries implications with regard to the common origin of exocrine and neuroendocrine cells in the gastrointestinal tract.

Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma

BACKGROUND Cervical esophageal carcinoma (CEC) is an uncommon malignancy. Limited data supports the use of definitive chemoradiotherapy (CRT) as primary treatment. Furthermore, the role of human papillomavirus (HPV) tumor infection in CEC remains unknown. This study retrospectively analyzes both outcomes of CEC patients treated with CRT and the incidence and potential role of HPV tumor infection in CEC lesions. METHODS A total of 37 CEC patients were treated with definitive CRT at our institution between 1987 and 2013. Of these, 19 had tumor samples available for high-risk HPV (types 16 and 18) pathological analysis. RESULTS For all patients (n=37), 5-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 34.1%, 40.2%, and 65.6%, respectively. On pathological analysis, 1/19 (5.3%) patients had an HPV-positive lesion. CONCLUSIONS Definitive CRT provides disease-related outcomes comparable to surgery. Moreover, HPV tumor infection in CEC is uncommon and its prognostic role is unclear. Our data contribute to the construction of an anatomical map of HPV tumor infection in squamous cell carcinomas (SCC) of the upper aerodigestive tract, and suggest a steep drop in viral infection rates at sites distal to the oropharynx, including the cervical esophagus.

Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma

An 82-year-old man presented with progressive right frontal headaches. The patients history was significant for benign polyps on surveillance colonoscopy 2 years prior, without high-grade dysplasia or carcinoma. MRI revealed an enhancing lesion arising within the superomedial aspect of the right orbit. Lesion biopsy demonstrated histological appearance and immunophenotype suggestive of colonic adenocarcinoma. Staging positron emission tomography/CT showed visceral metastases and diffuse activity in the posterior rectosigmoid, consistent with metastatic colon cancer. Treatment of the orbital lesion with external beam radiotherapy to 30 Gy resulted in significant palliation of the patients headaches. The patient expired 2 months following treatment completion due to disease progression. Orbital metastasis as the initial presentation of an occult colorectal primary lesion is exceedingly rare, and occurred in this patient despite surveillance colonoscopy. Radiotherapy remains an efficacious modality for treatment of orbital metastases.

Primary breast diffuse large B-cell lymphoma: treatment strategies and patterns of failure*

Abstract Treatment strategies and outcomes were assessed in 25 patients with primary breast diffuse large B-cell lymphoma (PB-DLBCL) treated between 1995 and 2016. We specifically investigated the timing of recurrence, and the roles of radiotherapy (RT) and central nervous system prophylaxis (CNS PPX). Fifty-two percent of patients received RT, and 28% received CNS PPX. Fourteen patients (56%) experienced recurrence, with 76% of relapses occurring ≥24 months after diagnosis, in contrast to reports supporting the use of 24-month event-free survival as a surrogate endpoint in the general DLBCL population. Use of RT was associated with a trend toward improved progression-free survival (PFS). Twenty percent of patients experienced CNS relapse, with no clear benefit to CNS PPX. These data emphasize the importance of long-term follow-up for PB-DLBCL patients, suggest a PFS benefit with the addition of RT, and highlight high rates of CNS relapse.

Omitting cardiophrenic lymph nodes in the treatment of patients with Hodgkin lymphoma via modified involved-site radiation therapy

Abstract Cardiophrenic lymph nodes (CPLNs) are occasionally involved in Hodgkin lymphoma (HL). We characterized the incidence of CPLN involvement among 169 HL patients and evaluated outcomes after treatment with omission of the CPLN region from the involved-site radiation therapy (ISRT) field. Three types of RT fields were used: standard (S)-ISRT, reduced-dose (RD)-ISRT (lower dose to CPLNs, standard to other sites), or modified (M)-ISRT (omission of CPLNs). CPLNs were involved at diagnosis in 29 patients (17%). Of the 20 patients who received RT after complete response to chemotherapy, 4(20%) received S-ISRT, 8(40%) RD-ISRT, and 8(40%) M-ISRT. The four-year progression-free survival was 94.7%. One relapse occurred at a non-CPLN site after RD-ISRT. The mean heart dose and volume of the heart that received 25 Gy was higher for S-ISRT patients compared to M-ISRT (p = .043 and p = .025, respectively). Re-planning the M-ISRT cases as S-ISRT resulted in significant increase in cardiac doses.

Highlighting the need for reliable clinical trials in glioblastoma

ABSTRACT Introduction: Several recent phase III studies have attempted to improve the dismal survival seen in glioblastoma patients, with disappointing results despite prior promising phase II data. Areas covered: A literature review of prior phase II and phase III studied in glioblastoma was performed to help identify possible areas of concern. Numerous issues in previous phase II trials for glioblastoma were found that may have contributed to these discouraging outcomes and discordant results. Expert commentary: These concerns include the improper selection of therapeutics warranting investigation in a phase III trial, suboptimal design of phase II studies (often lacking a control arm), absence of molecular data, the use of imaging criteria as a surrogate endpoint, and a lack of pharmacodynamic testing. Hopefully, by recognizing prior phase II trial limitations that contributed to failed phase III trials, we can adapt quickly to improve our ability to accurately discover survival-prolonging treatments for glioblastoma patients.

Evolution and Management of Treatment-Related Toxicity in Anal Cancer

Over the past several decades, clinical trials have demonstrated improved disease-related outcomes in the definitive treatment of anal cancer. Although treatment with radiation and concurrent chemotherapy results in high rates of cure, significant acute and late toxicities are seen. This review focuses on the evolution of treatment-related toxicity for anal cancer. Management of these adverse effects is reviewed, as are future directions in anal cancer treatment and their impact on toxicity.