Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer with or without induction chemotherapy.

BACKGROUND: To compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT). METHODS: 77 patients underwent definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event reporting system, short-term toxicity (T) scores were generated for IC (TIC), CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an overall score (Toverall) from treatment start to post treatment period. RESULTS: Acute toxicity other than dysphagia, odynophagia, or dermatitis was reported in 90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87, P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003). CONCLUSION: I/CCRT patients reported more cumulative acute toxicity during treatment compared to CCRT patients using the TAME reporting system.

Stepwise development of a cancer care delivery research study to evaluate the prevalence of virus infections in cancer patients.

BACKGROUND: SWOG initiated a cancer care delivery research study of virus infection rates among newly diagnosed cancer patients. This study will inform viral screening guidelines in oncology clinics. METHODS: In a first step 'vanguard' phase, we evaluated the feasibility of multiple study procedures. Site investigators were surveyed to obtain feedback on study implementation. RESULTS: Much higher enrollment occurred at sites where all physicians participated and viral testing was performed as routine practice. These procedures will be required going forward. Additional protocol changes based on site investigator input were implemented. CONCLUSION: This multistep protocol design process illustrates how cancer care delivery research studies can adapt to real-world strategies and procedures that exist at community clinics where the predominance of cancer patients are treated.

Prognostic factors for advanced-stage human immunodeficiency virus-associated classical Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine plus combined antiretroviral therapy: a multi-institutional retrospective study.

BACKGROUND: The treatment and outcomes of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HL) continue to evolve. The International Prognostic Score (IPS) is used to predict the survival of patients with advanced-stage HL, but it has not been validated in patients with HIV infection. METHODS: This was a multi-institutional, retrospective study of 229 patients with HIV-associated, advanced-stage, classical HL who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus combination antiretroviral therapy. Their clinical characteristics were presented descriptively, and multivariate analyses were performed to identify the factors that were predictive of response and prognostic of progression-free survival (PFS) and overall survival (OS). RESULTS: The overall and complete response rates to ABVD in patients with HIV-associated HL were 91% and 83%, respectively. After a median follow-up of 5 years, the 5-year PFS and OS rates were 69% and 78%, respectively. In multivariate analyses, there was a trend toward an IPS score >3 as an adverse factor for PFS (hazard ratio [HR], 1.49; P=.15) and OS (HR, 1.84; P=.06). A cluster of differentiation 4 (CD4)-positive (T-helper) cell count <200 cells/µL was associated independently with both PFS (HR, 2.60; P=.002) and OS (HR, 2.04; P=.04). The CD4-positive cell count was associated with an increased incidence of death from other causes (HR, 2.64; P=.04) but not with death from HL-related causes (HR, 1.55; P=.32). CONCLUSIONS: The current results indicate excellent response and survival rates in patients with HIV-associated, advanced-stage, classical HL who receive ABVD and combination antiretroviral therapy as well as the prognostic value of the CD4-positive cell count at the time of lymphoma diagnosis for PFS and OS.

The influence of limited English proficiency on outcome in patients treated with radiotherapy for head and neck cancer.

OBJECTIVE: To evaluate how limited English proficiency affects treatment outcome in head and neck cancer (HNC) patients treated with curative intent radiation therapy (RT). METHODS: From 2004 to 2010, 131 patients with HNC underwent RT. Patient's self-reported primary language and race/ethnicity were obtained at hospital registration. English proficiency was categorized as being English proficient (EP) or limited English proficient (LEP). Race/ethnicity was categorized as white, black and other (Hispanics and Asians). Patients were evaluated for locoregional (LRC), distant control (DC), overall (OS) and disease-free (DFS) survival. RESULTS: Fewer LEP patients (60.0%) underwent chemoradiation compared to EP (83.8%), P=0.028. The three-year actuarial LRC for EP and LEP patients was 82.2% and 58.3%, respectively, P=0.038. LEP patients had an increased risk of locoregional failure on univariate Cox regression analysis (hazard ratio, HR 2.4, 95% CI, 1.0-5.8). No differences by English proficiency were seen for DC, OS and DFS. Race/ethnicity was not associated LRC, DC, OS and DFS. CONCLUSION: Inferior locoregional control was observed in LEP patients receiving RT for HNC. Potential health disparities as a result of limited English proficiency require further investigation. PRACTICE IMPLICATIONS: Patient education, use of culturally sensitive interpreter and patient navigation services, and improved patient compliance should be considered in head and neck cancer patients receiving complex multidisciplinary care.

Cancer and men who have sex with men: a systematic review.

Disparities in cancer burden between specific populations are widely acknowledged, including differences associated with sexual orientation. We searched PubMed for articles about cancer in men who have sex with men. Of the 410 publications that we identified, 47 reports were eligible for inclusion and review. Most addressed issues of cancer prevention, followed by diagnosis, survivorship, detection, and cancer treatment. Disparities exist mainly in the prevalence of viruses linked to cancers. Knowledge about sexual orientation and cancer is skewed towards infection-related cancers, so information about the association between sexual orientation and other cancers, and social and cultural causes for disparities in cancer, is less available. Men who have sex with men are still a largely overlooked minority group in this respect. Future research should examine the effects of sexual orientation on cancer, from prevention to survivorship.

Human immunodeficiency virus-associated primary lung cancer in the era of highly active antiretroviral therapy: a multi-institutional collaboration.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at increased risk for primary lung cancer (LC). We wished to compare the clinicopathologic features and treatment outcome of HIV-LC patients with HIV-indeterminate LC patients. We also sought to compare behavioral characteristics and immunologic features of HIV-LC patients with HIV-positive patients without LC. PATIENTS AND METHODS: A database of 75 HIV-positive patients with primary LC in the HAART era was established from an international collaboration. These cases were drawn from the archives of contributing physicians who subspecialize in HIV malignancies. Patient characteristics were compared with registry data from the Surveillance Epidemiology and End Results program (SEER; n = 169,091 participants) and with HIV-positive individuals without LC from the Adult and Adolescent Spectrum of HIV-related Diseases project (ASD; n = 36,569 participants). RESULTS: The median age at HIV-related LC diagnosis was 50 years compared with 68 years for SEER participants (P < .001). HIV-LC patients, like their SEER counterparts, most frequently presented with stage IIIB/IV cancers (77% vs. 70%), usually with adenocarcinoma (46% vs. 47%) or squamous carcinoma (35% vs. 25%) histologies. HIV-LC patients and ASD participants had comparable median nadir CD4+ cell counts (138 cells/µL vs. 160 cells/µL). At LC diagnosis, their median CD4+ count was 340 cells/µL and 86% were receiving HAART. Sixty-three HIV-LC patients (84%) received cancer-specific treatments, but chemotherapy-associated toxicity was substantial. The median survival for both HIV-LC patients and SEER participants with stage IIIB/IV was 9 months. CONCLUSION: Most HIV-positive patients were receiving HAART and had substantial improvement in CD4+ cell count at time of LC diagnosis. They were able to receive LC treatments; their tumor types and overall survival were similar to SEER LC participants. However, HIV-LC patients were diagnosed with LC at a younger age than their HIV-indeterminate counterparts. Future research should explore how screening, diagnostic and treatment strategies directed toward the general population may apply to HIV-positive patients at risk for LC.

HIV-associated bladder cancer: a case series evaluating difficulties in diagnosis and management.

BACKGROUND: Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection. We sought to describe the clinical characteristics of HIV-associated bladder cancer. METHODS: A retrospective study was performed involving HIV-positive patients with bladder cancer, combining cases from multiple institutions with published case reports. Data regarding patient demographics, HIV status, clinical presentation, pathology, cancer treatment, and outcome were analyzed using descriptive statistics. RESULTS: Eleven patients were identified with a median age of 55 years (range, 33-67). The median CD4+ count at cancer diagnosis was 280 cells/mm3 (range, 106-572 cells/mm3). Six patients (55%) had a known risk factor for bladder cancer, and nine (82%) presented with hematuria. Ten patients had transitional cell carcinoma, and most had superficial disease at presentation. Treatment included mainly transurethral resection of bladder tumor followed by a combination of local and systemic therapies. One patient received intravesical bacillus Calmette-Guèrin (BCG) without complication. Several patients (55%) were alive following therapy, although many (64%) suffered from local relapse and metastatic disease. CONCLUSION: Bladder cancer is part of the growing list of cancers that may be encountered in patients living longer with chronic HIV-infection. Our patients presented at a younger age and with only mild immunosuppression, however, they experienced an expected course for their bladder cancer. Hematuria in an HIV-infected patient warrants a complete evaluation.

Human immunodeficiency virus-associated prostate cancer: clinicopathological findings and outcome in a multi-institutional study.

OBJECTIVE: To characterize the clinicopathological findings and the outcome of human immunodeficiency virus (HIV)-infected patients diagnosed and treated for prostate carcinoma, as HIV-positive men being treated with highly active antiretroviral therapy (HAART) are living longer and thus are more likely to develop cancers such as prostate cancer. PATIENTS AND METHODS: We performed a retrospective, multi-institutional study involving HIV-positive men with concomitant prostate carcinoma. We collected data regarding patient demographics (age, race), HIV status (CD4(+) cell count, HIV viral load, HAART), PSA level (at cancer diagnosis), symptoms and signs, radiological findings, pathology (Gleason score, stage), cancer treatment (type, side-effects), and outcome (response, survival). Accrued data was analysed using descriptive statistics. RESULTS: We identified 17 patients (mean age 59 years) with HIV-associated prostate adenocarcinoma. The mean CD4(+) count was 336 cells/mm(3) and the mean HIV viral load was 17 319 copies/mL. In all, 14 (82%) of these men were receiving HAART. Most patients were diagnosed with carcinoma after an abnormal screening PSA level. The mean PSA level was 30 ng/mL. Only six (35%) men had an abnormal prostate on examination. The mean Gleason score was 6.8, and in most cases, cancer was confined to the prostate gland. Most patients were amenable to curative treatment with hormonal therapy, radiation, and/or prostatectomy. There were no serious treatment related side-effects. One patient remained untreated. All treated patients had a complete response (undetectable PSA level). Most patients were long-term survivors. Documented death in five cases was unrelated to prostate cancer. CONCLUSION: The management of HIV-positive men with prostate carcinoma in the HAART era is becoming increasingly important. Our data shows that in men receiving HAART, their age, PSA levels, clinical presentation, management, and outcome from treated prostate carcinoma does not appear to be significantly altered by HIV status. Therefore, we recommend that patients with prostate cancer and well-controlled HIV viraemia be managed similarly to their HIV-negative counterparts.

HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is unusual in the general population aged <60 years. Various reports indicate a much higher incidence of monoclonal gammopathy among human immunodeficiency virus (HIV)-infected patients and a significantly younger age at diagnosis. We sought to describe the laboratory findings and clinical course of MGUS, including association with plasma cell disorders, other malignancies, and infections, in 25 HIV-infected patients with a detectable serum monoclonal protein. METHODS: We reviewed the patients' demographic characteristics, stage of HIV infection, and clinical course. Laboratory studies included determination of CD4(+) T lymphocyte cell counts, HIV type 1 loads, and quantitative immunoglobulin levels; serum and urine protein immunoelectrophoresis; and determination of serum viscosity indices. Skeletal surveys and bone marrow biopsies were performed in selected cases. RESULTS: Twenty-four of 25 patients were male, and the median age of patients was 50 years (range, 21-69 years). The median CD4(+) T lymphocyte count was 350 cells/ microL (range, 40-1029 cells/ microL; mean, 355 cells/ microL), and the median HIV load was <75 copies/mL (range, <50 to 100,000 copies/mL; mean, 20,800 copies/mL). Thirteen of 25 patients had HIV viremia, despite receiving highly active antiretroviral therapy (HAART). After a mean follow-up duration of 21 months, 7 patients (28%) received a diagnosis of a malignancy (multiple myeloma, in 1 patient; non-Hodgkin lymphoma, in 1; Hodgkin lymphoma, in 1; Kaposi sarcoma, in 2; and plasmacytoma, in 2). Ten patients were coinfected with hepatitis B virus and/or hepatitis C virus; 6 were anemic. No patients developed renal failure or hypercalcemia. Nine (56%) of 19 evaluable patients had a decrease of serum monoclonal protein (mean, 0.5 g/dL) while receiving HAART. CONCLUSIONS: Patients in our study were characterized by the detection of a monoclonal protein at a younger age and the increased presence of other viral infections (infection with hepatitis B or C virus or Kaposi sarcoma herpesvirus) than is typically seen in an HIV-uninfected cohort. CD4(+) T lymphocyte counts were relatively robust. HAART appeared to have a favorable impact on the serum monoclonal protein level in 9 patients. Long-term follow-up is needed to better define the natural history of MGUS and the link to other possible contributing factors.

Highly active antiretroviral therapy and viral response in HIV type 2 infection.

Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2. CD4+ cell count, HIV-2 virus load, and clinical status were found to correlate well, providing evidence that HIV-2 virus load is useful in managing treatment of patients with HIV-2 who are receiving therapy. However, HAART regimens with predicted efficacy for treatment of HIV type 1 infection are not as efficacious for treatment of HIV-2. Controlled clinical trials of HIV-2-infected patients receiving various HAART regimens are needed to provide therapeutic guidance to the medical community.

Non-AIDS-defining cancer in HIV-infected people.

Since the advent of HAART, the natural history of HIV disease has been changing, with decreased risk of life-threatening opportunistic infections and prolonged survival. Concurrently, a variety of non-AIDS-defining cancers have been reported with increased incidence in HIV-infected adults, including anal cancer, Hodgkin's disease, head and neck cancer, testicular cancer, lung cancer, colon cancer, basal cell cancer, squamous cell cancer of the skin, and melanoma. It appears that these tumors may have a more aggressive clinical course in HIV-infected people. Available data, however, suggest that antitumor response and survival in HIV-infected people with malignancy are improved in people with higher CD4 counts. The possible mechanisms for the increased incidence and altered clinical course of these malignancies in HIV-infected people remain unclear.

HIV and refractory anemia with excess blasts (RAEB).

We report the case of a 36 year old man who was hospitalized with pneumonia and pancytopenia with refractory anemia with excess blasts confirmed by bone marrow biopsy. He was subsequently found to have advanced HIV infection. Both the HIV infection and the myelodysplastic syndrome responded to highly active anti-retroviral therapy (HAART) with sustained normalization of his hematologic abnormalities within 79 days.

Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study.

PURPOSE: Liposomal anthracyclines and paclitaxel are considered the best available cytotoxic therapies for Kaposi's sarcoma (KS), but relapse is common. To identify new interventions for relapsed or progressive KS, a phase II study of low-dose etoposide to assess its toxicity and efficacy was conducted. PATIENTS AND METHODS: Thirty-six patients with high-risk KS were treated with oral etoposide 50 mg/d for 7 consecutive days of every 2-week cycle. All patients' disease had relapsed or progressed after prior combination chemotherapy or anthracycline therapy. For patients without a complete or partial response after two cycles of therapy and no toxicity greater than grade 2, the dose of etoposide was escalated to 100 mg/d orally on days 1 to 7 of each 14-day cycle. Treatment-related and disease-specific quality of life was evaluated using patient reports on the General Health Self-Assessment Form and a KS-specific measure. RESULTS: One patient achieved a complete response, 12 patients had a partial response (overall response rate, 36.1%), and stable disease was observed in 12 patients (33.3%). Tumor responses were seen in all disease sites. Fourteen patients had their dose escalated, of whom five responded. The median time to response was 17.7 weeks; the median duration of response was 25 weeks. The most frequent hematologic abnormality was neutropenia, which was grade 4 in seven patients and grade 3 in six. Opportunistic infections occurred in eight patients during the treatment period. Both response to treatment and toxicity influenced patient-reported quality of life. CONCLUSION: We conclude that low-dose oral etoposide at a dose of 50 mg/d is safe and effective for the treatment of refractory or progressed AIDS-related KS and has an overall positive effect on the quality of life of responding patients.

Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study.

PURPOSE: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are overexpressed in Kaposi's sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. RESULTS: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m(2)/d. Prior KS therapy was reported by 17 patients (94%). COL-3-related grade 3 or 4 adverse events were reported by six patients and included photosensitivity, rash, and headache. There was one complete response and seven partial responses, for an overall response rate of 44%, with a median response duration of 25+ weeks. The median COL-3 half-life was 39.3 hours (range, 4.1 to 251.1 hours). There was a significant difference between responders and nonresponders with respect to the change in MMP-2 serum levels from baseline to minimum value on treatment (P =.037). CONCLUSION: COL-3 administered orally once daily to patients with AIDS-related KS is reasonably well tolerated. The most common adverse event was dose-related photosensitivity. Antitumor activity was noted. Further evaluation of COL-3 for the treatment of KS is warranted.