John Ng

Minimizing second cancer risk following radiotherapy: current perspectives

Secondary cancer risk following radiotherapy is an increasingly important topic in clinical oncology with impact on treatment decision making and on patient management. Much of the evidence that underlies our understanding of secondary cancer risks and our risk estimates are derived from large epidemiologic studies and predictive models of earlier decades with large uncertainties. The modern era is characterized by more conformal radiotherapy technologies, molecular and genetic marker approaches, genome-wide studies and risk stratifications, and sophisticated biologically based predictive models of the carcinogenesis process. Four key areas that have strong evidence toward affecting secondary cancer risks are 1) the patient age at time of radiation treatment, 2) genetic risk factors, 3) the organ and tissue site receiving radiation, and 4) the dose and volume of tissue being irradiated by a particular radiation technology. This review attempts to summarize our current understanding on the impact on secondary cancer risks for each of these known risk factors. We review the recent advances in genetic studies and carcinogenesis models that are providing insight into the biologic processes that occur from tissue irradiation to the development of a secondary malignancy. Finally, we discuss current approaches toward minimizing the risk of radiation-associated secondary malignancies, an important goal of clinical radiation oncology.

Does adjuvant radiotherapy benefit patients with diffuse‐type gastric cancer? Results from the Surveillance, Epidemiology, and End Results database

Diffuse‐type gastric cancer is observed in approximately one‐third of gastric cancers, yet the optimal treatment remains controversial. In the recently published Intergroup 0116 trial, a subgroup analysis demonstrated a lack of a long‐term survival benefit for adjuvant chemoradiation therapy among patients with diffuse‐type gastric cancer.

Locally Advanced Pancreatic Adenocarcinoma: Update and Progress

Pancreatic cancer, the 4th leading cause of cancer death in the U.S., remains a challenging disease for the oncology community. Less than 20% of all cases are potentially cured by surgical resection, while the large majority of cases are deemed either unresectable or metastatic upon diagnosis. Advances in treating locally advanced pancreatic cancer have been few and modest. In this years American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, three abstracts (#252, #254, #313) were presented with novel approaches towards treating locally advanced pancreatic cancer. Surgery for recurrent disease, a promising new chemoradiation regimen, and the application of an exciting multi-agent regimen (FOLFIRINOX: oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in a non-clinical trial setting, highlight the novel approaches focused on the management of this difficult disease.

Locally Advanced Pancreatic Adenocarcinoma: Are We Making Progress?

Pancreatic cancer, as the 4th leading cause of cancer death in the U.S., remains a challenging disease for all oncologists. Less than 20% of all cases could be potentially cured by surgical resection, while the majority of cases are deemed either unresectable or metastatic upon diagnosis. In this years American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. The LAP-07 study, a large phase III study with two separate randomizations, updated their accrual status, but with no interim data yet reported (Abstract #e14619). A single institutional review study reported its promising results on the incorporation of interferon to chemoradiation, but the toxicities could be concerning (Abstract #e14648). Abstract #e14607 demonstrated promising survival data from a tri-modality approach incorporating local and systemic chemotherapy concurrent with external beam radiation as well as radiofrequency ablation. The tolerability of sorafenib in locally advanced pancreatic cancer was shown in a small phase I study (Abstract #e14525). CyberKnife® stereotactic body radiation therapy was investigated as a modality for local palliation (Abstract #e14506). More effective therapeutic agents and approaches are still needed in this difficult disease. This highlight article will focus on the management of locally advanced pancreatic cancer.

New Developments in the Management of Borderline Resectable Pancreatic Cancer

The optimal management of borderline resectable pancreatic cancer remains unclear. Neoadjuvant chemoradiation remains the most common approach in the United States, while neoadjuvant chemotherapy alone is also widely utilized and has demonstrated efficacy but there has been no clear consensus about a regimen that would be most beneficial in this setting. We will discuss three abstracts that were presented in the 2013 ASCO Gastrointestinal Cancers Symposium in which various regimens were evaluated in the neoadjuvant setting.

Is There a Role of Radiotherapy in the Management of Pancreatic Neuroendocrine Tumors (PNET)

Pancreatic neuroendocrine tumors (PNET) represent a heterogeneous group of tumors with varying tumor biology and prognosis. Advanced PNETs remain a difficult therapeutic challenge because of their high malignant potential and their resistance to conventional chemotherapy although there have been recent developments with promising results with the use of novel agents for the treatment of this disease. Combined modality chemoradiation is not widely used in the management of locally advanced pancreatic endocrine tumors. We discuss Abstract #335 from 2012 ASCO GI Cancers Symposium and share our experience to discuss efficacy and toxicity of concurrent capecitabine or infusional 5-fluorouracil and radiotherapy in patients with resected, locally advanced and metastatic PNET. Prospective studies to investigate the role of radiation and chemoradiation are warranted.

New tools and novel approaches in treating locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most aggressive malignant tumors and represents the fourth leading cause of cancer-related death. The median survival of locally advanced pancreatic carcinoma is ten to thirteen months. In this years American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. Wild et al. (Abstract #4055) explored a novel tool of selective delivery of TNF-alpha intratumoral injection. This approach limited the systemic toxicity, and suggested survival benefit in only the subgroup of patients with locally advanced pancreatic adenocarcinoma with stage T1-T3. Two studies were presented which were designed to assess the use of two novel agents, targeting signaling pathways, in addition to gemcitabine. Van Laethem et al. (Abstract #4050) are testing the MEK inhibitor, BAY 86-9766 in combination with gemcitabine. However, treatment related toxicity is still of concern. In the other study, Evans et al. (Abstract #TPS4134) are testing the combination of dasatinib and gemcitabine. This is a placebo-controlled, randomized, double blind phase II study. However, results are not available. Stereotactic body radiotherapy (SBRT) is an emerging technology with the comparative efficacy of single fraction radiotherapy (as is used in radiosurgery) vs. fractionated SBRT still unknown. Herman et al. (Abstract #4045) examined the role of fractionated SBRT in locally advanced pancreatic cancer. The phase II results showed a median overall survival of 15.9 months, suggesting that SBRT may be an emerging tool in the multi-modality treatment of locally advanced pancreatic cancer.

Exuberant Squamous Metaplasia with Calcification Following Intraoperative Radiotherapy for Breast Carcinoma: Report of an Unusual Case and Retrospective Review of Cases from a Single Institution

Intraoperative radiotherapy (IORT) is a novel and increasingly utilized radiation technique in the treatment of breast carcinoma. There are few reports on the histologic changes seen in breast tissue from patients who have undergone IORT. We sought to evaluate the histologic changes observed in specimens received following IORT, as well as report an unusual case which prompted our study. A retrospective review of patients who received IORT and subsequently had breast tissue histologically evaluated at our institution was performed. Fifteen post‐IORT specimens from 12 patients, including the patient from the reported case, were studied. We report a case of a 77‐year‐old woman found to have mammographic microcalcifications at the lumpectomy site 6 months following lumpectomy and IORT for ductal carcinoma in situ (DCIS). A stereotactic biopsy showed abundant desquamated anucleate squamous cells with calcification and keratin material associated with squamous metaplasia of ducts. Carcinoma was not present. The predominant findings in the post‐IORT specimens were fat necrosis and scar (n = 5), recurrent invasive carcinoma (n = 5), surgical site changes (n = 3), abscess (n = 1), and exuberant squamous metaplasia with calcification (n = 1). Five of fifteen (33%) post‐IORT specimens showed squamous metaplasia, all of which were collected within 6 months of IORT delivery. The morphologic changes observed after IORT are similar to those seen after external beam radiotherapy. Exuberant squamous metaplasia is an uncommon consequence of IORT; however, pathologists should be aware of this phenomenon and review a history of prior intraoperative radiation before raising concern for malignancy.