Cancer

doi: 10.1002/cncr.28200pmid: N/A

Clevenger, Lauren; Schrepf, Andrew; DeGeest, Koenraad; Bender, David; Goodheart, Michael; Ahmed, Amina; Dahmoush, Laila; Penedo, Frank; Lucci, Joseph; Thaker, Premal H.; Mendez, Luis; Sood, Anil K.; Slavich, George M.; Lutgendorf, Susan K.

doi: 10.1002/cncr.28188pmid: 23797955

BACKGROUND Sleep disturbance is a common clinical complaint of oncology patients and contributes to substantial morbidity. However, because most sleep studies have been cross‐sectional, associations between sleep quality and distress in patients with ovarian cancer over time remain unclear. This prospective longitudinal study examined rates of sleep disturbance; contributions of depression, anxiety, and medication use in sleep disturbance; and associations between sleep quality and quality of life (QOL) during the first year after diagnosis among women with ovarian cancer. METHODS Women with a pelvic mass completed measures of sleep quality, depression, anxiety, and QOL before surgery. Those diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal cancer repeated surveys at 6 months and 1 year after diagnosis. Mixed modeling was used to examine trajectories of psychosocial measures over time, as well as associations between changes in distress and sleep quality. Relationships between changes in sleep and QOL were also examined. RESULTS The majority of patients reported disturbed global sleep (Pittsburgh Sleep Quality Index > 5) at all 3 time points. Medications for sleep and pain were associated with worse sleep at all time points. Greater increases in depression were associated with increased disturbances in sleep quality over time (P < .04). Worsening sleep was also associated with declines in QOL over time (P < .001). CONCLUSIONS Sleep disturbance is common and persistent in women with ovarian cancer, and is linked to depressive symptoms and QOL. Pharmacologic treatment does not appear to adequately address this problem. Results highlight the need for ongoing screening and intervention for sleep disturbance in this population. Cancer 2013;119:3234–3241. © 2013 American Cancer Society.

Haymart, Megan R.; Banerjee, Mousumi; Yin, Huiying; Worden, Francis; Griggs, Jennifer J.

doi: 10.1002/cncr.28187pmid: 23839797

BACKGROUND Because anaplastic thyroid cancer is a rare malignancy with a high mortality rate, the benefit of multimodality treatment was evaluated. METHODS Overall survival was determined in the 2742 patients captured by the National Cancer Database who were diagnosed with anaplastic thyroid cancer between 1998 and 2008. Kaplan‐Meier analysis and then Cox proportional hazard regression was performed, controlling for patient characteristics and treatment. RESULTS Only older age (adjusted hazard ratio (AHR) for ≥ 85 years = 3.43, 95% confidence interval (CI) = 2.34‐5.03; for 75‐84 years, AHR = 2.85, 95% CI = 1.97‐4.11; for 65‐74 years, AHR = 2.20, 95% CI = 1.53‐3.15; for 45‐64 years, AHR = 2.08, 95% CI = 1.47‐2.95) and omission of treatment were associated with greater mortality (omission of surgery: AHR = 1.79, 95% CI = 1.61‐1.99; omission of radiation therapy: AHR = 1.56; 95% CI = 1.41‐1.73; and omission of chemotherapy: AHR = 1.28, 95% CI = 1.15‐1.43). In subgroup analysis of patients with American Joint Committee on Cancer stage IVA, IVB, and IVC anaplastic thyroid cancer, combination therapy with surgery, radiation, and chemotherapy was associated a difference in median survival of months. CONCLUSIONS Multimodality management of anaplastic thyroid cancer results in a marginal treatment benefit. The poor overall survival of all anaplastic thyroid cancer patients, regardless of treatment, emphasizes the need for informed patients whose preferences are incorporated into treatment decision‐making. Cancer 2013;119:3133–3139. © 2013 American Cancer Society.

Dang, Nguyen D.; Dang, Phuong‐Thanh; Samuelian, Jason; Paulino, Arnold C.

doi: 10.1002/cncr.28198pmid: 23744806

BACKGROUND Paratesticular rhabdomyosarcoma (PTRMS) is the most common primary solid tumor arising from the mesenchymal tissue of the testis. Traditionally, retroperitoneal lymph node dissection is not recommended for children aged <10 years because of the morbidity of the procedure and low risk of retroperitoneal lymph node involvement. In the current study, the authors analyzed the patient and tumor characteristics of PTRMS as well as survival outcomes associated with lymph node dissection status. METHODS A total of 255 cases of PTRMS were identified from the patient data reported by the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973 through 2009. RESULTS Among 173 patients aged ≥10 years, lymph node dissection was found to improve the 5‐year overall survival (OS) rate from 64% to 86% (P < 0.01). Conversely, patients aged <10 years fared extremely well regardless of lymph node dissection status; the 5‐year OS rate was 100% and 97%, respectively, for patients who did versus those who did not undergo lymph node dissection (P = .37). The yield of positive lymph nodes was approximately ≥ 20% when < 11 lymph nodes were removed. The incidence of lymph node involvement was also higher in older patients compared with younger patients (40% vs 8%). Radiotherapy improved the OS rate in patients with lymph node involvement (5‐year OS rate: 90% with vs 36% without radiation; P < .0001). CONCLUSIONS Lymph node dissection is recommended in patients aged ≥10 years. Radiotherapy is beneficial in patients with lymph node‐positive disease. Cancer 2013;119:3228–3233. © 2013 American Cancer Society.

Yendamuri, Sai; Huang, Miriam; Malhotra, Usha; Warren, Graham W.; Bogner, Paul N.; Nwogu, Chukwumere E.; Groman, Adrienne; Demmy, Todd L.

doi: 10.1002/cncr.28099pmid: 23719932

BACKGROUND Signet ring cell esophageal adenocarcinoma histology has been difficult to study in single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was examined to assess the prognostic implications of this esophageal adenocarcinoma subtype. METHODS All patients with esophageal adenocarcinoma in the SEER database from 2004 to 2009 were included. Univariate and multivariate analyses examining the relationship of signet ring cell histology with overall survival were performed in all patients, as well as those undergoing surgical resection. RESULTS A total of 596 of 11,825 (5%) study patients had signet ring cell histology. Patients with signet ring cell histology were similar in age, race, and sex distribution, but had a higher grade (P < .001) and higher stage (P < .001) at diagnosis. In both the all‐patient group as well as those undergoing surgical resection, univariate analyses showed a worse survival in patients with signet ring cell esophageal cancer (hazard ratio (HR) = 1.24; 95% confidence interval (CI) = 1.13‐1.36 and HR = 1.57; 95% CI = 1.29‐1.93, respectively). In multivariate analyses adjusting for covariates, patients with signet ring cell cancer had a worse prognosis than those without (HR = 1.18; 95% CI = 1.07‐1.30). In surgically resected patients, this remained a trend, but did not reach statistical significance (HR = 1.16; 95% CI = 0.94‐1.42). CONCLUSIONS This large study of esophageal adenocarcinoma confirms the clinical impression that signet ring cell variant of adenocarcinoma is associated with an advanced stage at presentation and a worse prognosis independent of stage of presentation. Cancer 2013;119:3156–3161. © 2013 American Cancer Society.

Squires, Malcolm H.; Fisher, Sarah B.; Fisher, Kevin E.; Patel, Sameer H.; Kooby, David A.; El‐Rayes, Bassel F.; Staley, Charles A.; Farris, Alton B.; Maithel, Shishir K.

doi: 10.1002/cncr.28175pmid: 23719746

BACKGROUND Excision repair cross‐complementing gene‐1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are associated with overall survival (OS) in several malignancies. Their expression patterns and prognostic value in resected gastric adenocarcinoma (GAC) are not known. METHODS In total, 109 patients who underwent resection for GAC between January 2000 and June 2011 had tissue available for analysis. The primary objective was to assess for the differential expression of ERCC1 and TS using immunohistochemistry. The secondary objective was to assess for the association between OS and the expression of ERCC1 and TS. RESULTS The median follow‐up was 21.2 months, and the median OS was 28.8 months. Resected GAC exhibited differential expression of ERCC1 (high expression, 23%; n = 25) and TS (high expression, 43%; n = 47). ERCC1 and TS expression were not associated with OS. In a subset analysis of patients who received chemotherapy (n = 73), high ERCC1 expression was associated with decreased OS (16.7 months vs 53.8 months; P = 0.03). After controlling for known adverse pathologic features, high ERCC1 expression persisted as a negative prognostic factor in multivariate Cox regression analysis (hazard ratio, 2.5; 95% confidence interval, 1.03‐6.0; P = .04). Conversely, in patients who underwent resection only (n = 35), high ERCC1 expression demonstrated a trend toward improved OS (40.4 months vs 12.7 months; P = .10); a positive prognostic influence also was present on multivariate analysis (hazard ratio, 0.20; 95% confidence interval, 0.04‐0.86; P = .03). CONCLUSIONS Resected GAC exhibited differential expression of TS and ERCC1. Among all patients, ERCC1 and TS expression levels were not associated with OS. High ERCC1 tumor expression was associated with decreased OS in the patients who received chemotherapy but was associated with increased OS in those who underwent surgery alone. ERCC1 expression had prognostic value in resected gastric cancer, and further investigation is warranted. Cancer 2013;119:3242–3250. © 2013 American Cancer Society.

Colbert, Lauren E.; Fisher, Sarah B.; Hardy, Claire W.; Hall, William A.; Saka, Burcu; Shelton, Joseph W.; Petrova, Aleksandra V.; Warren, Matthew D.; Pantazides, Brooke G.; Gandhi, Khanjan; Kowalski, Jeanne; Kooby, David A.; El‐Rayes, Bassel F.; Staley, Charles A.;

Shah, Anand; Hahn, Stephen M.; Stetson, Robert L.; Friedberg, Joseph S.; Pechet, Taine T. V.; Sher, David J.

doi: 10.1002/cncr.28131pmid: 23720093

BACKGROUND The traditional treatment for clearly operable (CO) patients with stage I non–small cell lung cancer (NSCLC) is lobectomy, with wedge resection (WR) and stereotactic body radiation therapy (SBRT) serving as alternatives in marginally operable (MO) patients. Given an aging population with an increasing prevalence of screening, it is likely that progressively more people will be diagnosed with stage I NSCLC, and thus it is critical to compare the cost‐effectiveness of these treatments. METHODS A Markov model was created to compare the cost‐effectiveness of SBRT with WR and lobectomy for MO and CO patients, respectively. Disease, treatment, and toxicity data were extracted from the literature and varied in sensitivity analyses. A payer (Medicare) perspective was used. RESULTS In the base case, SBRT (MO cohort), SBRT (CO cohort), WR, and lobectomy were associated with mean cost and quality‐adjusted life expectancies of $42,094/8.03, $40,107/8.21, $51,487/7.93, and $49,093/8.89, respectively. In MO patients, SBRT was the dominant and thus cost‐effective strategy. This result was confirmed in most deterministic sensitivity analyses as well as probabilistic sensitivity analysis, in which SBRT was most likely cost‐effective up to a willingness‐to‐pay of more than $500,000/quality‐adjusted life year. For CO patients, lobectomy was the cost‐effective treatment option in the base case (incremental cost‐effectiveness ratio of $13,216/quality‐adjusted life year) and in nearly every sensitivity analysis. CONCLUSIONS SBRT was nearly always the most cost‐effective treatment strategy for MO patients with stage I NSCLC. In contrast, for patients with CO disease, lobectomy was the most cost‐effective option. Cancer 2013;119:3123–3132. © 2013 American Cancer Society.

Hwang, E. Shelley; Clarke, Christina A.; Gomez, Scarlett Lin

doi: 10.1002/cncr.28181pmid: 23824869

Garrison, Louis P.; Lalla, Deepa; Brammer, Melissa; Babigumira, Joseph B.; Wang, Bruce; Perez, Edith A.

doi: 10.1002/cncr.28196pmid: 23775560

BACKGROUND Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests are commonly used to assess human epidermal growth factor 2 (HER2) status of tumors in patients with breast cancer. This analysis evaluates the likely cost‐effectiveness of expanded retesting to assess HER2 tumor status in women with early stage breast cancer. METHODS We developed a decision‐analytic model to estimate the incremental cost‐effectiveness ratio (ICER) of expanded reflex testing from a US payer perspective. Expanded reflex testing is defined as retesting tumor specimens from patients whose tumors are IHC0, IHC1+, or FISH‐negative on their first test. In the base case, we assumed that 80% of patient tumors are initially IHC‐tested and 20% are FISH‐tested. Testing outcomes for IHC and FISH with and without retesting were based on published meta‐analyses. The cost of tests and treatment and the long‐term health outcomes were obtained from the literature. RESULTS In the base case, we estimated that 2.27% of women who received expanded reflex testing would be HER2‐positive and receive trastuzumab treatment: the projected ICER was $36,721 per life year or $39,745 per quality‐adjusted life year (QALY). This varied between $47,100 per QALY and $35,500 per QALY if we assumed that 1%‐8% of patients retested were then HER2+, respectively. The results of deterministic and probabilistic sensitivity analysis were robust. This strategy would result in 4700 (2000‐17,000) patients being eligible to receive trastuzumab treatment annually. CONCLUSIONS Retesting patients who are IHC0, IHC1+, or FISH‐negative is projected to be a cost‐effective clinical strategy. Cancer 2013;119:3113–3122. © 2013 American Cancer Society.