Risk Of Contralateral Disease Research Articles

Risk and Rate of Occult Contralateral Nodal Disease in Surgically Treated Patients With Human Papillomavirus−Related Squamous Cell Carcinoma of the Base of the Tongue

The optimal treatment strategy for patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) of the base of the tongue (BOT) has not been sufficiently studied. To investigate the rate of and risk factors for occult contralateral nodal disease in patients with HPV-related BOT OPSCC undergoing transoral surgery and bilateral neck dissections. This retrospective case series reviewed the medical records of patients with HPV-related BOT OPSCC who underwent transoral surgery and bilateral neck dissections from January 1, 2002, through December 31, 2018, at the tertiary care center of Washington University School of Medicine in St Louis. Patients had a median follow-up of 30.0 months (interquartile range, 11.0-60.4 months). Patients with recurrent disease or multiple synchronous OPSCC primary tumors were excluded for a total of 89 patients. Data were analyzed from January 1 through June 1, 2019. The primary outcome was the rate of contralateral occult nodal disease. Secondary outcomes were potential risk factors for contralateral occult nodal disease and regional recurrence rates. Eighty-nine patients were included in the series, of whom 81 (91.0%) were men. The mean (SD) age was 60 (9) years. Overall, 34 patients (38.2%) had pathologic contralateral nodal metastases. Seventy patients had no clinical evidence of contralateral nodal disease. Of these 70, occult nodes were identified in 15 (21.4%). Risk of contralateral disease was higher when the primary tumor crossed midline (odds ratio, 6.23; 95% CI, 1.71-22.77). Of the 55 patients with no occult disease identified, only 2 (3.6%) received radiotherapy to the contralateral neck, and no regional recurrence of disease was noted. Given the rate of occult contralateral nodal disease of 21.4%, it appears that contralateral elective neck dissection or radiotherapy should be recommended in patients with HPV-related BOT OPSCC. Patients with a pathologically negative result of contralateral neck dissection may not benefit from radiotherapy to that nodal basin. Future prospective investigations should evaluate functional and oncologic outcomes of contralateral elective neck dissection compared with elective radiotherapy in the contralateral neck for HPV-related BOT OPSCC.

Discussions about contralateral prophylactic mastectomy among surgical oncology providers and women with sporadic breast cancer: a content analysis.

Rates of contralateral prophylactic mastectomy (CPM) have risen substantially, yet little is known about how and to what extent CPM is discussed within surgical oncology visits at the time of treatment decision-making. We examined CPM discussions in naturally occurring interactions between sporadic breast cancer patients and their surgical oncology providers. Women with early-stage unilateral disease were recruited before their first surgical visit and completed brief questionnaires to determine study eligibility and interest in treatment options. After their visits, enrolled patients and their providers completed questionnaires assessing discussion of and interest in CPM. Audio-recorded visits from 36 unique patients were randomly selected, transcribed, and analyzed. A CPM discussion was present in 28 transcripts. Approximately half of CPM discussions were initiated by the patient or the oncology provider. The topic of CPM was most frequently introduced while reviewing available treatment options. Patients were most interested in pursuing CPM to reduce the risk of future breast cancer. Providers most frequently responded by offering information (e.g., about risk of contralateral disease). A high level of agreement was found among patient, provider, and observer ratings of whether or not CPM was discussed. CPM discussions were consistently present within our sample. Results can be used to build providers' skills and bring provider-patient communication more in line with best practices and recommendations from leading professional medical societies.

Nanotamoxifen Delivery System: Toxicity Assessment After Oral Administration and Biodistribution Study After Intravenous Delivery of Radiolabeled Nanotamoxifen.

Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m (99mTc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.

Is contralateral prophylactic mastectomy (CPM) overused? Results from a population-based study.

26 Background: The growing rate of CPM among women diagnosed with breast cancer has raised concerns about potential for over-treatment yet, little is known about factors that affect the decisions for this surgical treatment option. Methods: We surveyed 2,245 women newly diagnosed with breast cancer and reported to the Detroit and Los Angeles SEER registries from 6/05-2/07. We merged these data to SEER and re-surveyed them again approximately 4 years later (n=1,525). The primary outcome was receipt of CPM. We modeled surgical treatment decision making in two stages: any mastectomy (including CPM) vs. lumpectomy, and CPM vs. unilateral mastectomy (UM) among mastectomy-treated patients. The primary independent variable was clinically significant risk of developing contralateral disease (family history of at least 2 family members with breast cancer and/or a positive genetic test). We also evaluated the degree to which worry about recurrence drove initial treatment decisions (very vs. somewhat/not at all) and controlled for race/ethnicity, age, stage and SEER site. Results: Of the 1,446 women who had not had a recurrence of breast cancer by the time 2 survey, 35% considered CPM and 7.4% received it. Among those who received a mastectomy for the affected breast the figures were 53% and 19%, respectively. About 70% of patients who received CPM were clinically at very low risk for contralateral disease. 90% of those who got CPM reported being very worried about recurrence when making their treatment decision, compared to 80% of those who received UM (p<0.05). Multivariate regression showed that receipt of CPM vs. UM was associated with having a family history (OR 5.1; 95% CI: 2.49-10.1) and a positive genetic test (OR: 10.93; 95% CI: 3.37-35.71), but was also associated with greater worry about recurrence (OR: 2.07; 95% CI: 1.01-4.51). Conclusions: Many women considered CPM despite the fact that very few of them had clinically significant risk of contralateral breast cancer. Most women who had CPM did not have a clinical indication for considering it and thus not expected to benefit in terms of disease free survival. More research is needed about the underlying factors driving decision-making for CPM.

Invasive lobular breast cancer - No increased risk of contralateral disease

Invasive lobular breast cancer - No increased risk of contralateral disease

P1-08-10: Invasive Lobular Breast Cancer – No Increased Risk of Contralateral Disease.

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for up to 14% of invasive breast cancers. Worldwide the incidence of breast cancer is increasing each year. Large population based studies using the Surveillance, Epidemiology, and End results (SEER) data have shown that the incidence of ILC has increased from 1977 to 1995. ILC has historically been thought to be associated with an increased risk of developing contralateral breast cancer and this belief may, in part, be responsible for the increasing trend towards contralateral prophylactic mastectomy. Methods: All female patients diagnosed with breast cancer during the time period 1998–2003 were identified from two large cancer registries, Northern and Yorkshire Cancer Registry and Information Service (NYCRIS) and West Midlands Cancer Intelligence Unit (WMCIU). All patients diagnosed with either Infiltrating duct(adeno) carcinoma, microinvasive ductal carcinoma, infiltrating ductular carcinoma (all classified as ‘ductal') or lobular (adeno)carcinoma were included. Patients with a mixed type of breast cancer were excluded from the analysis. Follow-up was complete until October 2010. Data were compiled for diagnosed contralateral breast cancer of any histological type. Results: Of the 32,735 patients with invasive ductal cancer 898 (2.74%) developed a contralateral breast cancer. In comparison 166 (3.1%) of 5397 patients with lobular cancer developed a contralateral breast cancer. The median time to first contralateral event was equivalent for both morphologies (ductal 40 months and lobular 39 months). Conclusion: This study suggests that there is no increased risk for developing a contralateral breast cancer in patients diagnosed with an invasive lobular breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-10.

P4-11-10: Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic Mastectomy among Young Women with Breast Cancer.

Abstract Background: There has been an increasing prevalence of contralateral prophylactic mastectomy (CPM), particularly among younger women with breast cancer. There has been limited research evaluating patient preference, knowledge and decision-making regarding this issue. Methods: We surveyed women who had bilateral mastectomy who were enrolled in a multicenter, longitudinal cohort study of women diagnosed with breast cancer at age 40 and younger. The CPM survey included 23 items on decision making, knowledge, and satisfaction with CPM. Results: Of the 550 patients enrolled as of November 2010, 157 (28.5%) had bilateral mastectomy, of whom 124 completed the CPM survey (response rate 79%). Women with bilateral breast cancer (3) or bilateral prophylactic (1) indications for surgery were excluded. Median age at diagnosis was 37 years (range 26–40); 26 women (21%) reported having a genetic mutation (21 BRCA1 and 5 BRCA2). Excluding mutation carriers, women estimated that a median of 10 of 100 women (range 0–90) would develop contralateral breast cancer in the 5 years after unilateral breast cancer treatment and that 5 of 100 women (range 0 — 98) treated with CPM would develop contralateral breast cancer. Eighteen percent of all respondents believed that women who undergo bilateral mastectomy live longer. Women were asked the importance of potential reasons for undergoing CPM (see Table 1). Eighty-two percent of women were “extremely confident” in their decision to undergo CPM and 92% would “definitely” still choose CPM. Conclusion: Young women with breast cancer have high rates of CPM. Many young women who have undergone CPM overestimate the risk of contralateral disease and the benefits of CPM, including believing that CPM will prevent metastasis and extend life. Interventions to counsel young women with early breast cancer to help them make optimal surgical treatment decisions are needed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-10.

Genetic Basis of Bilateral Renal Cancer: Implications for Evaluation and Management

Kidney cancer is estimated to affect more than 54,000 individuals in the United States each year and to be responsible for 13,000 deaths in the United States annually. When a patient with localized kidney cancer is treated surgically, 5and 10-year disease-specific survival can approach 95%. However, despite the remarkable recent advances in targeted therapeutics for kidney cancer, this disease is still fatal for the majority of patients who present with advanced disease. In this issue of Journal of Clinical Oncology, Wiklund et al report an elegant study of the risk of bilateral kidney cancer. In this population-based study from Norway and Sweden, the authors defined the risk of development of bilateral kidney cancer in 28,642 patients observed for an average of 4.4 years. They found asynchronous renal cell cancer in 86 patients. One hundred twelve metachronous bilateral kidney cancer cases were detected during 126,493 person years of follow-up, revealing an overall relative risk of 3.1, with a cumulative incidence of 0.85 after 20 or more years of follow-up. A striking observation in the current work was the finding of a significant increase in relative risk of bilateral disease for young patients diagnosed with this kidney cancer. When compared with the general population, Wiklund et al found a 90% increase in risk for contralateral disease when a patient 60 years or older was diagnosed with kidney cancer, whereas in patients younger than 40 years of age, there was an 1,800% increased risk for the development of cancer in the remaining kidney. This article raises a number of important issues in the evaluation and management of patients with kidney cancer. Does bilateral disease represent metastasis of the cancer from one kidney to the other, or does it result from a genetic predisposition? In some patients with widespread metastatic disease, metastases may account for tumors in the contralateral kidney. However, in the great majority of patients, the multiple/bilateral tumors seem to arise independently, as occurs in a number of the inherited forms of kidney cancer, such as von HippelLindau (VHL) and Birt-Hogg-Dube syndrome (Table 1). It is also likely that in most instances of nonfamilial bilateral, multifocal kidney cancer, the tumors arise independently. Wiklund et al report on the incidence of bilateral kidney cancer; however, because of the magnitude and nature of this large study, the authors were not able to categorize the tumors by histologic type or to assess the prevalence of multifocality within an individual kidney. If a tumor is bilateral, it is, by definition, multifocal. The nature of this large study likely underestimates the true incidence of bilateral kidney cancer (given that the surveillance was limited to 4 years) and it is likely that in many of the patients there was occult intrarenal multifocality. The finding of bilateral tumors in such a large percentage of patients with this disease suggests that these patients have a genetic predisposition to develop renal cell cancer, and that a single gene alteration is responsible for the development of each of the tumors. This raises the possibility that many patients carry a hereditary predisposition to develop kidney tumors, and their management should be based on the expectation that additional kidney tumors may develop in these patients. If so, removing the entire kidney may be suboptimal, because much of the remaining kidney at the time of surgery may be disease free and functional, and it may be needed in the future. It has been estimated that 5% to 10% of renal cancers are hereditary. However, 5% to 10% is most likely a significant underestimate of the true hereditary predisposition to renal cancer Important insight into this question comes from the study of Gudbjartsson et al, who studied all patients in Iceland who had renal cancer from 1955 to 1999. When Gudbjartsson et al evaluated whether these individuals with kidney cancer had a relative with kidney cancer, they found a much higher risk in first-degree relatives as well as a significantly higher risk for renal cancer in members of the extended family of an affected individual. The Icelandic study suggests that there may be a genetic predisposition in nearly 60% of patients with kidney Table 1. Hereditary Renal Cancer Syndromes

Should screening MRI be included in surveillance for patients treated with breast-conserving therapy?

Breast MRI has been shown to provide diagnostic benefit in multiple situations. It has proved useful in the evaluation of ruptured silicone implants and in the evaluation of patients with cancerous axillary lymph nodes, a negative mammogram and unremarkable physical examination. Gorechlad et al. carried out a retrospective study designed to determine whether MRI has a role in screening for cancer recurrence in patients treated with breast-conserving therapy. As the results showed that the recurrence rate and risk of contralateral disease were both very low, the authors concluded that MRI screening would not have been cost-effective and was unlikely to have improved overall survival.