Selecting a comparison group for 5-year oral and pharyngeal cancer survivors: two methods.

BACKGROUND: To assess potential long-term consequences of cancer treatment, studies that include comparison groups are needed. These comparison groups should be selected in a way that allows the subtle long-range effects of cancer therapy to be detected and distinguishes them from the effects of aging and other risk factors. The purpose of this investigation was to test two methods of recruiting a comparison group for 5-year oral and pharyngeal cancer survivors (peer-nominated and listed sample) with emphasis on feasibility and the quality of the match. METHODS: Participants were drawn from a pool of 5-year survivors treated at a large Southeastern hospital. A peer-nominated sample was solicited from the survivors. A listed sample matched on sex, age, and zip code was purchased. Telephone interviews were conducted by a professional call center. RESULTS: The following represent our key findings: The quality of matching between survivors and listed sample was better than that between survivors and peer-nominated group in age and sex. The quality of matching between the two methods on other key variables did not differ except for education, with the peer method providing a better match for the survivors than the listed sample. The yield for the listed sample method was greater than for the peer-nominated method. The cost per completed interview was greater for the peer-nominated method than the listed sample. CONCLUSION: This study not only documents the methodological challenges in selecting a comparison group for studies examining the late effects of cancer treatment among older individuals but also documents challenges in matching groups that potentially have disproportionate levels of comorbidities and at-risk health behaviors.

Salivary IgA is not a reliable indicator of upper respiratory infection in collegiate female soccer athletes.

It has been shown that mucosal immunity measures such as salivary immunoglobulin A (s-IgA) can be affected by sport activities and has resulted in an increased susceptibility to infection. However, there is limited research that has evaluated the change in s-IgA throughout a full sport training season. The purpose of the study was to evaluate the change in s-IgA levels and incidence of upper respiratory infection in the National Collegiate Athletic Association Division I level female soccer athletes compared to age matched controls over an entire sport training season. Saliva samples were collected from 12 randomly selected female collegiate soccer athletes and 8 age-matched controls. Samples were collected bimonthly from the athletes' pre-and post-sport training sessions and pre- and post-90-minute sedentary period for the controls. Analysis showed there was a significant (p < 0.05) group × time interaction in total protein (TP) for collections 1 and 4 and a significant (p < 0.05) group × time interaction in s-IgA/TP for collections 2 and 3. There was no significant difference (p > 0.05) between athletes and controls for s-IgA or total symptom days (TSDs). Furthermore, there was no significant correlation between absolute s-IgA and TSDs or s-IgA/TP and TSDs throughout the sport training season. The large range of measurable levels for s-IgA at the different time points for athletes and controls and the lack of relationship between s-IgA levels and TSDs indicate that s-IgA is not an appropriate measure to determine an athlete's susceptibility to during a training season.

Managing cetuximab hypersensitivity-infusion reactions: incidence, risk factors, prevention, and retreatment.

Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody approved by the US Food and Drug Administration for the treatment of colorectal (CRC) and head and neck (H&N) cancers. Hypersensitivity-infusion reactions (HIRs) confer moderate morbidity and potential mortality. HIRs have a wide geographic incidence with few identifiable risk factors. Limited data regarding risk-reduction interventions for HIR or post-HIR retreatment are available. All patients treated with cetuximab at a single Veterans Affairs facility were monitored for development of HIRs, with baseline clinical, demographic, and supportive care data recorded. All received standard premedication based on cohort assignment. A total of 51 consecutive patients (30 CRC; 21 H&N) received at least one dose of cetuximab. Grades II-IV HIRs occurred in 14 patients (27%; 6 grade II, 6 grade Ill, 2 grade IV). There was no grade V HIR. All HIRs occurred during the first infusion. There were no differences between age, race, diagnosis, stage, concurrent chemotherapy, or radiotherapy with cetuximab, allergy history, or military service era of patients developing HIRs versus those who did not.There were no identifiable risk factors that predicted the severity of HIR. Neither premedication modifications (P = 0.34) nor bronchodilator use (P= 0.12) impacted the incidence or severity of HIR. A cetuximab test dose successfully elicited an HIR and resulted in an 87% cost savings. None of five patients receiving subsequent retreatment with anti-EGFR MoAb had recurrence of an HIR. An HIR during cetuximab infusion can be a serious and underestimated toxicity. The relatively high incidence reported here is consistent with that previously identified in the Southeastern United States. No clinical, demographic, or historic variables reliably predicted HIR in our population. Use of a test dose to elicit a HIR appears to be feasible and cost-effective. Use of panitumumab after a cetuximab HIR in select patients with CRC appears to be feasible and safe.

The effects of aerobic interval training on the left ventricular morphology and function of VLCAD-deficient mice.

This study examined the effect of aerobic interval training on cardiac adaptations in VLCAD-deficient mice and determined the effects of the deficiency on the morphology and function of the left ventricle among 53 knockout homozygous VLCAD-/-, 28 heterozygous VLCAD±, and 39 controls VLCAD+/+ male mice (129 SvJ/C57BL6). Echocardiographic images were used to determine the left ventricular (LV) wall thicknesses, during systole and diastole, acquired at a depth setting of 20 mm. Cardiac hypertrophy (as evidenced by increased wall thickness, and decreased left ventricular dimension in diastole and systole) appeared to be a major finding in the VLCAD-/- mouse with, however, normal %FS. The trained mice from all three genotypes exhibited lower body weight compared with their controls. The echocardiographic data of this study demonstrated structural but not functional differences among the three genotypes. This study demonstrated that VLCAD± deficient mice handled interval training similarly to the non-deficient mice. Four VLCAD-/- deficient mice died unexpectedly on the treadmill during the early stages of training. The VLCAD-/- deficient mice that survived adapted to the aerobic interval training similarly to the non-deficient mice. It is unclear whether aerobic interval training is an appropriate training tool for the VLCAD-deficient humans.

Altered fractionation and/or adjuvant chemotherapy in definitive irradiation of squamous cell carcinoma of the head and neck.

OBJECTIVE: To review the roles of altered fractionation and adjuvant chemotherapy in the treatment of patients with squamous cell carcinomas of the head and neck. STUDY DESIGN: Review of the pertinent literature. METHODS: The literature pertaining to altered fractionation and/or adjuvant chemotherapy for patients with squamous cell carcinomas of the head and neck was reviewed to define the optimal combination of radiotherapy and adjuvant chemotherapy. RESULTS: The efficacy of altered fractionation compared with conventional fractionation depends on the fractionation schedule employed. Some hyperfractionated and accelerated fractionation schedules have resulted in improved locoregional control but no significant improvement in overall survival. In contrast to induction and maintenance chemotherapy, concomitant chemotherapy appears to result in improved locoregional control and survival. CONCLUSIONS: Altered fractionation and/or concomitant chemotherapy results in improved locoregional control and, in some instances, survival for patients with advanced head and neck cancer. Depending on primary site, the applicability of these aggressive treatment regimens is limited by an enhanced probability of severe complications as tumor volume increases. The optimal combination of these modalities is unclear and will be defined by future prospective trials.

Primary Pulmonary Synovial Sarcoma during Pregnancy: A Diagnostic and Therapeutic Dilemma.

Synovial sarcoma is a rare soft tissue sarcoma that typically arises in the extremities of young adults. We report a case of a 26-year-old pregnant woman with biopsy-proven primary synovial sarcoma of the lung that was treated with chemotherapy with radiographic response. This is only the third documented case of primary pulmonary synovial sarcoma occurring during pregnancy and the first case where chemotherapy was given.

Racial disparity in oral and pharyngeal cancer in Florida in 1991-2008: mixed trends in stage of diagnosis.

OBJECTIVES: To explore changes in distribution of stage at diagnosis among individuals with oral and pharyngeal cancers over the past two decades and whether the changes differ by race. METHODS: We obtained 1991-2008 cancer incidence data for nine anatomic sites of the oral and pharyngeal structure from the Florida Cancer Data System. These cancers were grouped into oral squamous cell carcinoma (SCC), pharyngeal SCC, and other head and neck cancers. Annual percent change was calculated for each group to characterize trends in age-adjusted cancer incidence over time by race and stage at diagnosis. RESULTS: During 1991-2008, the overall age-adjusted oral SCC incidence was decreasing for both races, with a greater decline observed among Blacks. There was a large drop in incidence of regional-stage diagnoses among Blacks. For pharyngeal SCC, the age-adjusted incidence of localized- and regional-stage diagnoses was increasing for Whites during 1991-2008, with the largest increase in the incidence of regional-stage diagnoses. The percentage of localized-stage diagnoses was increasing for both races for oral SCC. A slight increase in percentage of localized-stage diagnoses was observed for Blacks for pharyngeal SCC, whereas no obvious change was observed among Whites. CONCLUSIONS: Blacks continued to have lower percentages of localized-stage diagnoses than Whites for nearly all sites, but an increasing percentage of localized-stage diagnoses was observed for oral SCC among Blacks. For pharyngeal SCC, the increase in incidence among Whites was accompanied by an increasing percentage of late-stage diagnoses. Coordinated public health approaches with a special emphasis on screening underserved populations are needed.

Altered fractionation and adjuvant chemotherapy for head and neck squamous cell carcinoma.

BACKGROUND: The aim of this review was to discuss the role of altered fractionation and adjuvant chemotherapy for patients treated with definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). METHODS: This review explores the pertinent literature and discusses the optimal management of previously untreated patients with stage III-stage IVA and/or -B HNSCCs. RESULTS: Depending on the schedule, altered fractionation improves locoregional control and survival. Both hyperfractionation and concomitant boost RT improve locoregional control and are associated with improved overall survival (OS). Adjuvant chemotherapy improves OS; the greatest impact is observed after concomitant versus induction or maintenance chemotherapy. Monochemotherapy appears to be equivalent to polychemotherapy. Drugs associated with the greatest survival benefit include fluorouracil and cisplatin. Intraarterial chemotherapy offers no advantage over intravenous chemotherapy. Concomitant cetuximab and RT results in improved outcomes similar to those observed after concomitant cisplatin-based chemotherapy and RT. CONCLUSIONS: Altered fractionation and/or concomitant chemotherapy result in improved outcomes compared with conventionally fractionated definitive RT alone for stage III-stage IV HNSCC. The optimal combination of RT fractionation and chemotherapy remains unclear.

Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer.

BACKGROUND: Both concomitant chemotherapy and altered fractionation radiotherapy (RT) have been shown to improve outcomes for patients with locoregionally advanced head and neck squamous cell carcinomas. However, both strategies also increase acute toxicity, and it is questionable whether the 2 can be safely combined. Traditional concomitant chemotherapy regimens include high-dose cisplatin given at 100 mg/m2 every 3 weeks. The authors' purpose was to report efficacy and toxicity after weekly cisplatin (30 mg/m2/wk) concurrent with altered fractionation RT. METHODS: One hundred twenty-one patients with American Joint Committee on Cancer stages II (3%), III (13%), or IV (84%) squamous cell carcinomas of the oropharynx (70%), hypopharynx (20%), or larynx (10%) were treated between 2000 and 2006 at the University of Florida with hyperfractionated RT (55 patients) or concomitant boost RT (66 patients) and concomitant cisplatin (30 mg/m2/wk). RESULTS: Median follow-up was 2.9 years; median follow-up on survivors was 3.6 years. Seventy-nine percent of patients completed ≥6 cycles of chemotherapy; 94% received ≥7200 centigrays. Seven (6%) patients changed from cisplatin to carboplatin because of bone marrow toxicity. Gastrostomy tube feeding was required in 54% of patients either before (16%) or during RT (38%). Two (1.6%) patients died from therapy-related complications. The 5-year outcomes were: local control, 83%; locoregional control, 79%; distant metastasis-free survival, 88%; cause-specific survival, 76%; and overall survival, 59%. Seven (6%) patients had severe late complications. Three (3%) patients required a permanent gastrostomy tube. CONCLUSIONS: Concomitant weekly cisplatin with altered fractionation RT is a safe and effective treatment regimen.

Definitive altered fractionation radiotherapy and concomitant weekly cisplatin for locally advanced head and neck cancer.

BACKGROUND: The purpose of this study was to determine the efficacy and toxicities of single-agent weekly cisplatin for patients with squamous cell carcinoma of the head and neck treated definitively with radiation therapy (RT). METHODS: Thirty-five patients with American Joint Committee of Cancer stage II (3%), stage III (14%), or stage IV (83%) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated from June 2000 to November 2003 at the University of Florida were retrospectively reviewed. Subjects received radiation therapy (RT; median, 74.4 Gy) and cisplatin, 30 mg/m2/wk. Altered fractionation was used in 34 of 35 (97%) patients. The endpoints were best response, percentage of grade III or IV toxicities, local-regional control, disease-free survival, cause-specific survival, and overall survival. RESULTS: The median number of cycles of cisplatin administered was 6. Grade III or IV toxicities were: anemia, 11%; thrombocytopenia, 6%; leukopenia, 26%; and mucositis, 23%. No patients had renal failure and 1 patient (3%) died because of therapy-related complications. Responses to therapy included 71% complete response, 17% partial response, and 6% stable disease. Median follow-up for all patients was 1.8 years (range, 0.1-7.8 years); median follow-up for living patients was 4.4 years (range, 2.6-7.8 years). The 3-year outcomes were: local-regional control, 85%; disease-free survival, 56%; cause-specific survival, 59%; and overall survival, 40%. CONCLUSION: Concomitant weekly CDDP with definitive RT is feasible, tolerable, highly active, and comparable with more complex, costly, and toxic regimens. Intercurrent disease was a significant contributor to mortality in our population. Our regimen is an attractive alternative to sequential chemoradiotherapy programs.

Sinonasal undifferentiated carcinoma.

PURPOSE: The purpose of this paper is to discuss the treatment and outcomes for patients with sinonasal undifferentiated carcinoma. METHODS: Review of the pertinent literature. RESULTS: Most series contain a limited number of patients treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up periods for disease-free patients are sometimes relatively short. The majority of patients present with locally advanced tumors; 10% to 30% have clinically positive regional nodes. The risk of local-regional recurrence after treatment is probably 20% to 30% or higher, depending on the extent of disease. The likelihood of distant dissemination is approximately 25% to 30% and the cure rate varies from roughly 20% to 50%. Better outcomes are observed in patients treated with craniofacial resection combined with pre- or postoperative RT alone or with adjuvant chemotherapy. This is probably due, in part, to selection bias. Patients with incompletely resectable tumors are best treated with definitive RT and adjuvant chemotherapy. CONCLUSION: The optimal treatment is craniofacial resection combined with adjuvant RT alone or with chemotherapy. The risk of relapse is relatively high and the probability of cure is modest. Patients with incompletely resectable tumors may sometimes be cured with definitive chemoradiation.

Merkel cell carcinoma of the skin with leptomeningeal metastases.

Merkel cell carcinoma is a rare skin tumor that is thought to arise from epithelial cells that have undergone neuroendocrine differentiation. It usually presents in older adults and has a slight male predominance. The most frequent site of occurrence is in the head and neck. It is an aggressive disease that has a high rate of local-regional and distant recurrence. Optimal treatment is controversial but generally consists of surgery and adjuvant radiotherapy. The role of chemotherapy is less defined. This report documents the first known case of Merkel cell carcinoma with perineural spread to the central nervous system with leptomeningeal dissemination. Whether this represents a more aggressive variant is unknown. Regardless, this pattern of spread is likely a rare event.

Adult head and neck soft tissue sarcomas.

BACKGROUND: The purpose was to determine the optimal treatment for adult patients with head and neck soft tissue sarcomas. METHODS: We conducted a review of the pertinent literature. RESULTS: Local control after surgery alone or combined with radiotherapy was obtained in approximately 60% to 70% of the patients. The probability of local control is influenced by histologic grade, tumor size, and surgical margins. Patients with high-grade tumors and/or positive margins have improved local control if adjuvant radiotherapy is used. Distant metastases occurred in 10% to 30% of patients. The 5-year overall and cause-specific survival rates varied from approximately 60% to 70% and are affected by age, histologic grade, previous treatment of tumor, invasion of deep structures, and adequacy of surgery. CONCLUSIONS: The optimal treatment for adult head and neck soft tissue sarcomas is surgery. Adjuvant radiotherapy improves outcomes for those with high-grade tumors and/or positive margins. Radiotherapy alone will cure a small subset of patients with unresectable tumors.

Squamous cell carcinoma of the anal margin.

PURPOSE: To define the optimal treatment of patients with squamous cell carcinoma (SCCA) of the anal margin. METHODS: Nineteen patients treated with curative intent by radiotherapy (RT) alone or combined with adjuvant chemotherapy (CTX) between 1979 and June 2000 were analyzed. The pertinent literature was reviewed and discussed as it related to our experience. RESULTS: Local control after RT or RT and CTX was observed in all 19 patients (100%). One T1 patient developed inguinal lymph node metastases and subsequently died secondary to regional and distant disease. This patient did not receive elective inguinal node RT; the lymph nodes of the other 18 patients in this analysis were irradiated. Four patients died of intercurrent disease at 25, 29, 37, and 113 months after RT, respectively. The remaining 14 patients were alive and disease-free from 52 to 143 months after treatment. No patient suffered a severe complication or required a diverting colostomy or an abdominoperineal resection (APR) after treatment. Review of the literature reveals that the probability of cure is similar after RT alone or combined with CTX compared with surgery. Therefore, the choice of treatment depends on the anticipated functional result. CONCLUSIONS: Patients with SCCA of the anal margin have a high likelihood of cure with sphincter preservation after RT or RT and CTX. Patients with well to moderately differentiated T1 tumors may undergo excision if it can be accomplished without compromising the sphincter. The remainder are treated with RT. Adjuvant CTX is indicated for those with T3-T4 tumors and/or involved regional nodes.