Human immunodeficiency virus-associated lung cancer in the era of highly active antiretroviral therapy

BACKGROUND:

Lung cancer is the leading cause of death among non‐acquired immunodeficiency syndrome (AIDS)‐defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era.

METHODS:

HIV‐positive patients who were diagnosed with lung cancer at the authors' institution during the HAART era (1995‐2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. The CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cutoff points (50 cells/mL, 200 cells/mL, and 500 cells/mL). Pearson correlation coefficients were estimated for each covariate studied. Survival was determined by using the Kaplan‐Meier method.

RESULTS:

Of 80 patients, 73 had nonsmall cell lung cancer. Baseline characteristics were as follows: median patient age, 52 years; male, 80%; African Americans, 84%; injection drug users, 25%; smokers, 100%; and previous exposure to antiretroviral agents, 55%. At the time of cancer diagnosis, the mean CD4 count was 304 cells/mL, and the mean viral load was 82,420 copies/mL. The latency between HIV diagnosis and lung cancer diagnosis was significantly shorter among women (4.1 years vs 7.7 years; P = .02), and 71% of patients received anticancer therapy. The 1‐year and 3‐year survival rates for stage IIIB/IV were 25% and 0%, respectively. Grade 3/4 toxicities occurred in 60% of patients who received chemoradiation versus 36% of patients who received chemotherapy. Cancer‐related survival was better for patients with CD4 counts >200 cells/mL (P = .0298) and >500 cells/mL (P = .0076).

CONCLUSIONS:

The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for patients with lung cancer who have HIV remain poor, a high CD4 count was associated with improved lung cancer‐related survival. Cancer 2012;. © 2011 American Cancer Society.     

Completion of and early response to chemoradiation among human immunodeficiency virus (HIV)-positive and HIV-negative patients with locally advanced cervical carcinoma in South Africa

BACKGROUND:

Very few published studies have dealt with the management of locally advanced cervix carcinoma among human immunodeficiency virus (HIV)‐positive patients. The objective of this study was to compare the clinical characteristics, radiation and chemotherapy treatments, and outcomes in a cohort of HIV‐positive and HIV‐negative women with cervical cancer.

METHODS:

The authors reviewed the charts of 59 HIV‐positive patients and 324 HIV‐negative patients who had stage IB1 to IIIB cervical carcinoma and who received radiation therapy. Demographic and clinical characteristics were compared at the time of diagnosis; and radiation doses, chemotherapy cycles, and responses were compared at the time of brachytherapy and at 6‐week follow‐up. Logistic regression models of response to treatment were developed.

RESULTS:

Forty‐nine HIV‐positive patients (88.1%) but only 213 HIV‐negative patients (65.7%) presented with stage IIIB disease (P = .009). Forty‐seven HIV‐positive patients (79.7%) and 291 HIV‐negative patients (89.8%) completed the equivalent dose of 68 Grays (Gy) external‐ beam radiation and high‐dose‐rate brachytherapy. (P = .03). Of the 333 patients who commenced concurrent chemotherapy, 26 HIV‐positive patients (53.1%) and 212 HIV‐negative patients (74.6%) completed ≥4 weekly cycles of platinum‐based treatment. Follow‐up was censured at 6 weeks. In models that included age, disease stage, HIV status, and treatment, a poor response at 6 weeks was associated only with stage IIIB disease (odds ratio, 2.39; 95% confidence interval, 1.45‐3.96) and receiving an equivalent radiation dose in 2‐Gy fractions of <68 Gy (OR, 3.14; 95% CI, 1.24‐7.94).

CONCLUSIONS:

HIV‐positive patients fared worse than HIV‐negative patients because of later presentation and a decreased likelihood of completing treatment. The current findings emphasize the importance of completing irradiation therapy. Further studies will address the association of these variables with survival. Cancer 2011. © 2011 American Cancer Society.     

Dose‐intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status

BACKGROUND:

The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity of human immunodeficiency virus (HIV)‐positive and HIV‐negative patients with BL who were treated in an intensive immunochemotherapy‐based and age‐adapted trial.

METHODS:

A total of 118 adult patients (80 HIV‐negative and 38 HIV‐positive) aged 15 to 83 years were treated with 4 (nonbulky stages I‐II) or 6 (stages II bulky, III‐IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years.

RESULTS:

The clinical characteristics of HIV‐positive patients were comparable with those who were HIV‐negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow‐up of 2.5 years, nonsignificant differences were observed in the 4‐year disease‐free survival and overall survival (OS) probabilities (77% and 63% for HIV‐positive and 80% and 78% for HIV‐negative patients, respectively). Young HIV‐infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%.

CONCLUSIONS:

Age‐adapted intensive immunochemotherapy is highly effective in both HIV‐negative and HIV‐positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival. Cancer 2013. © 2013 American Cancer Society.     

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus‐associated Kaposi sarcoma

BACKGROUND:

Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)‐associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined.

METHODS:

Patients with advanced HIV‐associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m² intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m² iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle.

RESULTS:

The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression‐free survival (17.5 months vs 12.2 months; P = .66), and 2‐year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077).

CONCLUSIONS:

Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV‐associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society.     

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma

BACKGROUND:

Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R‐EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)‐associated, aggressive B‐cell, non‐Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.

METHODS:

The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV‐associated NHL who received either R‐CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R‐EPOCH (n = 51; AMC034). Age‐adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R‐CHOP vs R‐EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event‐free survival (EFS) and overall survival (OS).

RESULTS:

Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R‐EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment‐associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P < .01).

CONCLUSIONS:

The current analysis provided additional level 2 evidence supporting the use of concurrent R‐EPOCH in patients with HIV‐associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R‐EPOCH with R‐CHOP in immunocompetent patients with diffuse large B‐cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society.     

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab

BACKGROUND:

Diffuse large B‐cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R‐CHOP)‐treated DLBCL cases.

METHODS:

Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R‐CHOP–treated patients.

RESULTS:

MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non‐GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors.

CONCLUSIONS:

Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high‐risk patients with poor prognosis. Cancer 2012. © 2011 American Cancer Society.     

The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers

BACKGROUND:

We assessed the efficacy of taxane chemotherapy in BRCA1‐ and BRCA2‐associated patients compared with sporadic metastatic breast cancer patients.

METHODS:

Response rates (RRs) to and progression‐free survival (PFS) after taxane chemotherapy of 35 BRCA1‐associated and 13 BRCA2‐associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third).

RESULTS:

Among BRCA1‐associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P = 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)‐negative patients, BRCA1‐associated patients (n = 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P = 0.03) and a shorter PFS (1.8 vs 3.8 months; P = 0.004) compared with sporadic patients (n = 19). These outcomes in HRec‐positive patients were similar in BRCA1‐associated (n = 11) and sporadic (n = 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2‐associated patients, who were mainly HRec‐positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P = 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively).

CONCLUSIONS:

BRCA1‐associated, HRec‐negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec‐negative patients. HRec‐positive BRCA1‐ and BRCA2‐associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients. Cancer 2012;. © 2011 American Cancer Society.     

Long-term outcomes of neoadjuvant chemotherapy before chemoradiation for locally advanced pancreatic cancer

BACKGROUND:

Neoadjuvant chemotherapy before chemoradiation therapy (CRT) may improve outcomes for patients with locally advanced pancreatic cancer, but optimal management remains controversial, and prior reports have limited follow‐up.

METHODS:

Seventy consecutive patients with unresectable (n = 46) or borderline resectable (n = 24) locally advanced pancreatic cancer were treated with CRT from 2005 to 2009. Patients typically received 50.4 grays in 28 fractions (91%) with concurrent 5‐fluorouracil (84%) or capecitabine (14%). Forty patients received CRT alone, and 30 patients received neoadjuvant chemotherapy before CRT for a median of 4 months, typically gemcitabine (93%). All patients without progression after neoadjuvant chemotherapy were offered CRT.

RESULTS:

Median follow‐up was 14.2 months (range, 3‐57 months). Fifty‐three percent of patients in the CRT group versus 83% in the neoadjuvant chemotherapy before CRT group had unresectable tumors at diagnosis; after completion of CRT, 20% of patients in both groups underwent resection. Compared with CRT alone, the neoadjuvant chemotherapy before CRT group demonstrated improved median overall survival (OS; 18.7 vs 12.4 months; P = .02) and progression‐free survival (11.4 vs 6.7 months; P = .02). On multivariate analysis, receipt of neoadjuvant chemotherapy (adjusted hazard ratio [HR], 0.49; 95% CI, 0.28‐0.87; P = .02) and surgical resection (adjusted HR, 0.38; 95% CI, 0.17‐0.85; P = .02) were associated with increased OS.

CONCLUSIONS:

Gemcitabine‐based neoadjuvant chemotherapy confers a significant OS advantage by allowing the selection of patients who will derive greatest benefit from CRT. Median survival with this approach was similar to that seen with surgical resection. Cancer 2012;118: 3026–35. © 2011 American Cancer Society.     

Treatment of human immunodeficiency virus-associated hodgkin disease is there a clue regarding the cause of hodgkin disease?

Background. The occurrence of human immunodeficiency virus (HIV)-associated Hodgkin disease (HD) offers a unique opportunity to study the cause of HD and compare HIV–HD with the well-characterized HIV–non-Hodgkin lymphoma (NHL). Methods. Eight patients with HIV–HD and 17 with HIV–NHL were treated. Results. The complete remission (CR) rate in HIV–HD was 100% with mechlorethamine, vincristine, procarbazine, and prednisone or doxorubicin, bleomycin, vinblastine, and dacarbazine (median survival, > 38.0 months). HIV–NHL patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CR, 80%; median survival, 13.0±1.3 months). Durable CR was achieved with one to six cycles of chemotherapy (median, 4). There were no late relapses. The difference between the survival rate associated with chemotherapy-treated HIV–HD and chemotherapy-treated HIV–NHL approached statistical significance (P = 0.06). Analysis indicated that all patients with HIV–HD (n = 8) may have acquired HIV through intravenous drug abuse (IVDA) compared with 1 of 17 patients with HIV–NHL (P = 0.0001). A combined analysis (metaanalysis) of 157 patients with chemotherapy-treated HIV–NHL and 51 with chemotherapy-treated HIV–HD confirmed the significantly better survival of those with HIV–HD (P < 0.0001). Conclusions. Standard combination chemotherapy, truncated as necessary, offers survival outcomes that are at least equivalent and, perhaps, superior to previously published experimental approaches for HIV–NHL and HIV–HD. HIV–HD has a significantly better prognosis than HIV–NHL and is associated with IVDA. These data suggest that the etiologic agents of HIV–HD and HIV–NHL may be transmissible, identifiable, and unique.     

Prognostic value of MYC rearrangement in cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma

BACKGROUND:

B‐cell lymphoma, Unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B‐cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms.

METHODS:

The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B‐cell lymphoma treated with either a standard DLBCL regimen (R‐CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone‐related therapy]) or more intensive regimens, such as R‐hyper‐CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high‐dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings.

RESULTS:

Thirty (58%) unclassifiable B‐cell lymphomas had MYC abnormalities (MYC⁺) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC⁺ and MYC^? groups were similar in their age distribution and International Prognostic Index scores. Progression‐free survival of patients with MYC⁺ unclassifiable B‐cell lymphoma treated initially with R‐CHOP was significantly worse than patients treated with R‐hyper‐CVAD (P = .0358). In contrast, for the MYC^? unclassifiable B‐cell lymphoma group, some patients responded to R‐CHOP, and others were refractory to R‐hyper‐CVAD.

CONCLUSIONS:

MYC aberrations are common in unclassifiable B‐cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R‐CHOP. In contrast, MYC^? unclassifiable B‐cell lymphoma patients responded variably to either R‐CHOP or aggressive therapy, and the latter showed no survival advantage. Cancer 2011;. © 2011 American Cancer Society.     

Long‐term incidence of cervical cancer in women with human immunodeficiency virus

BACKGROUND:

The objective of this study was to estimate the incidence of invasive cervical cancer (ICC) in women with human immunodeficiency virus (HIV) and compare it with the incidence in HIV‐uninfected women.

METHODS:

In a cohort study of HIV‐infected and uninfected women who had Papanicolaou tests obtained every 6 months, pathology reports were retrieved for women who had biopsy results or a self‐report of ICC. Histology was reviewed when reports confirmed ICC. Incidence rates were calculated and compared with those in HIV‐negative women.

RESULTS:

After a median follow‐up of 10.3 years, 3 ICCs were confirmed in HIV‐seropositive women, and none were confirmed in HIV‐seronegative women. The ICC incidence rate was not found to be associated significantly with HIV status (HIV‐negative women [0 of 100,000 person‐years] vs HIV‐positive women [21.4 of 100,000 person‐years]; P = .59). A calculated incidence rate ratio standardized to expected results from the Surveillance Epidemiology and End Results database that was restricted to HIV‐infected Women's Interagency HIV Study participants was 1.32 (95% confidence interval, 0.27‐3.85; P = 0.80).

CONCLUSIONS:

Among women with HIV in a prospective study that incorporated cervical cancer prevention measures, the incidence of ICC was not significantly higher than that in a comparison group of HIV‐negative women. Cancer 2009. Published 2009 by the American Cancer Society.     

Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study

BACKGROUND:

Urothelial carcinoma of the upper urinary tract (UUT‐UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High‐risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk, postsurgical UUT‐UC patients.

METHODS:

Using a multi‐institutional, international retrospective database, identified were 627 patients with high risk UUT‐UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included.

RESULTS:

Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow‐up was 22.5 months. The 5‐year, overall survival for the entire cohort was 43%, the 5‐year recurrence‐free survival was 54%, and metastasis‐free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer‐specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer‐specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5).

CONCLUSIONS:

Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;. © 2011 American Cancer Society.     

Elevated pretreatment serum concentration of YKL‐40—An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer

BACKGROUND:

The glycoprotein YKL‐40 is synthesized both by cancer cells and by tumor‐associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL‐40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL‐40 has not been established in nonsmall cell lung cancer (NSCLC).

METHODS:

Pretreatment serum levels of YKL‐40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41‐76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV disease. Ninety‐eight patients received combined gemcitabine and vinorelbine, and 91 received combined gemcitabine, vinorelbine, and cisplatin as first‐line chemotherapy. The median overall survival was 37 weeks.

RESULTS:

Patients had a median serum YKL‐40 level of 209 ng/mL (range, 19‐2153 ng/mL). No correlation was observed between overall survival and the type of chemotherapy regimen used, tumor stage, sex, or histologic types. Patients with high serum YKL‐40 levels (greater than the median level for all patients [209 ng/mL]) had a significantly shorter survival than patients with serum YKL‐40 levels below the median (median survival, 32 weeks vs 41 weeks; P = .007). In multivariate analysis, the serum YKL‐40 level, the presence of bone lesions, and the serum lactate dehydrogenase level were independent, statistically significant prognostic factors.

CONCLUSIONS:

The pretreatment serum YKL‐40 level was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010. © 2010 American Cancer Society.     

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation

BACKGROUND:

It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT.

METHODS:

The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor‐prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5‐fluorouracil, hydroxyurea, and a third agent.

RESULTS:

One hundred sixty‐six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow‐up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2‐year rates for OS, disease‐free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty‐three patients (19.9%) died of treatment‐related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2‐year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full‐dose ReRT, and radiotherapy interval.

CONCLUSIONS:

CReRT achieved a long‐term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients. Cancer 2011;. © 2011 American Cancer Society.     

Platinum/taxane‐based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma

BACKGROUND:

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients.

METHODS:

A retrospective, multi‐institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane–based chemotherapy (CT) ± RT.

RESULTS:

The authors identified 142 patients with a median follow‐up of 37 months (range, 7‐144 months). Thirty‐three patients were observed, 20 received RT alone, and 89 received CT ± RT. Twenty‐five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy‐treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT ± RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT‐ and CT + RT–treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression‐free survival (PFS) and cause‐specific survival (CSS) for chemotherapy‐treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five‐year PFS and CSS rates were 81.5% and 87.6% in CT ± RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS.

CONCLUSIONS:

Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well‐staged patients treated with platinum/taxane–based chemotherapy. This multi‐institutional study is the largest to support systemic therapy for early stage UPSC patients. Cancer 2009. © 2009 American Cancer Society.     

Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery

BACKGROUND:

The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC).

METHODS:

A retrospective review of stage III NSCLC patients treated at who were treated at the Dana‐Farber Cancer Institute/Brigham and Women's Cancer Center was done with institutional review board approval. Patients were followed for toxicity, local and distant failure, and overall survival. Multivariate Cox logistic regression analysis was used to determine the factors associated with treatment outcome.

RESULTS:

Between August 2000 and November 2006, 144 patients received concurrent chemoradiation (CRT) for stage III NSCLC. Eighty of 144 patients were men (56%), and the median age was 61 years (range, 33‐81 years). Sixty‐two patients (43%) had stage IIIA NSCLC, and 82 patients (57%) had stage IIIB NSCLC. Radiotherapy (RT) was given concurrently with chemotherapy to all patients; 100 patients (69%) received CRT without surgery, and 44 patients (31%) received with neoadjuvant CRT followed by surgical resection. The median RT dose was 60 grays (Gy) (range, 46‐70 Gy). The median follow‐up was 15 months (range, 3‐64 months), the median potential follow‐up was 37 months (range, 12‐84 months), and the median overall survival was 22 months (95% confidence interval, 15‐28 months). The 1‐year and 2‐year survival rates were 68% and 47%, respectively. Among the 44 patients who underwent resection, the median survival was 61 months, and the 2‐year survival rate was 73%. On multivariate analysis, stage at the time of treatment (stage IIIA vs stage IIIB) and use of surgery were the only factors associated with improved outcome (P = .01 and P = .001, respectively).

CONCLUSIONS:

In this retrospective series, those patients who were able to undergo resection appeared to have improved outcome after induction CRT. Cancer 2009. © 2009 American Cancer Society.     

Survival outcomes with the use of surgery in limited‐stage small cell lung cancer

BACKGROUND:

Although chemotherapy and radiation therapy currently are recommended in limited‐stage small cell lung cancer (L‐SCLC), several small series have reported favorable survival outcomes in patients who underwent surgical resection. The authors of this report used a US population‐based database to determine survival outcomes of patients who underwent surgery.

METHODS:

The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients who were diagnosed with L‐SCLC between 1988 and 2002 coded by SEER as localized disease (T1‐T2Nx‐N0) or regional disease (T3‐T4Nx‐N0). Kaplan‐Meier and Cox regression analyses were used to compare overall survival (OS) for all patients.

RESULTS:

In total, 14,179 patients were identified, including 863 patients who underwent surgical resection. Surgery was associated more commonly with T1/T2 disease (P < .001). Surgery was associated with improved survival for both localized disease and regional disease with improvements in median survival from 15 months to 42 months (P < .001) and from 12 months to 22 months (P < .001), respectively. Lobectomy was associated with the best outcome (P < .001). Patients with localized disease who underwent lobectomy with had a median survival of 65 months and a 5‐year OS rate of 52.6%; whereas patients who had regional disease had a median survival of 25 months and a 5‐year OS rate of 31.8%. On multivariate analysis, the benefit of surgery varied in a time‐dependant fashion. However, the benefit of lobectomy remained across all time intervals (P = .002).

CONCLUSIONS:

The use of surgery, and particularly lobectomy, in selected patients with L‐SCLC was associated with improved survival outcomes. Future prospective studies should consider the role of surgery as part of the multimodality management of this disease. Cancer 2010. © 2010 American Cancer Society.     

A phase 2 clinical trial of nab‐paclitaxel in previously treated and chemotherapy‐naive patients with metastatic melanoma

BACKGROUND:

nab‐Paclitaxel (ABI‐007, Abraxane), a 130‐nM, albumin‐bound (nab) particle form of Cremophor‐free paclitaxel, is approved for metastatic breast cancer. In the current study, the efficacy and safety of nab‐paclitaxel were evaluated in previously treated and chemotherapy‐naive patients with metastatic melanoma (MM).

METHODS:

Patients with histologically or cytologically confirmed, measurable MM were enrolled. nab‐Paclitaxel was administered intravenously weekly for 3 of 4 weeks at a dose of 100 mg/m² (in previously treated patients) or 150 mg/m² (in chemotherapy‐naive patients).

RESULTS:

Thirty‐seven patients were treated in each cohort. The response rate was 2.7% in the previously treated cohort and 21.6% in the chemotherapy‐naive cohort; the response plus stable disease rate was 37.8% and 48.6% in the previously treated and chemotherapy‐naive cohorts, respectively. The median progression‐free survival (PFS) was 3.5 months and 4.5 months, and the median survival was 12.1 months and 9.6 months, respectively. The probability of being alive and free of disease progression at 6 months was 27% for the previously treated cohort and 34% for the chemotherapy‐naive cohort; the probability of surviving 1 year was 49% and 41%, respectively, for the previously treated and chemotherapy‐naive cohorts. Approximately 78% of the previously treated patients and 49% of the chemotherapy‐naive patients were treated without dose reduction. Eight (22%) chemotherapy‐naive patients discontinued therapy because of toxicities. Drug‐related toxicities included grade 3 to 4 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neuropathy, alopecia, neutropenia, and fatigue.

CONCLUSIONS:

nab‐Paclitaxel was found to be well tolerated and demonstrated activity in both previously treated and chemotherapy‐naive patients with MM. The response rate, PFS, and survival compared favorably with current standard dacarbazine therapy and combination therapies for melanoma. nab‐Paclitaxel therapy of MM should be investigated further in controlled clinical trials. Cancer 2010. © 2010 American Cancer Society.     

The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States

BACKGROUND:

Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).

METHODS:

The authors analyzed population‐based registry linkage data from the US HIV/AIDS Cancer Match Study (1980‐2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category.

RESULTS:

Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5‐4.3). Although HCC incidence increased steadily across calendar periods (P_trend < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5‐3.9) between the monotherapy/dual therapy era (1990‐1995) and the recent highly active antiretroviral therapy era (2001‐2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (P_trend < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8‐2.8).

CONCLUSIONS:

HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV‐infected population. Cancer 2012. Published 2012 by the American Cancer Society.     

Hormone-receptor expression and activity of trastuzumab with chemotherapy in HER2-positive advanced breast cancer patients

BACKGROUND:

The relationship between quantitative immunohistochemical hormone receptor expression and response to the combination of trastuzumab with chemotherapy in HER2‐positive advanced breast cancer is currently unknown.

METHODS:

Estrogen receptor (ER) and progesterone receptor expression was studied both as a dichotomous variable (positivity set at ≥1% of positive cells) and as a continuous variable. The effect of hormone receptor expression on overall response rate and progression‐free survival in patients receiving trastuzumab‐based treatment was studied by univariate and multivariate analysis.

RESULTS:

One hundred eleven of 227 consecutive advanced breast cancer patients treated at 2 Institutions had hormone receptor‐positive tumors (49%). High expression of ER (≥30% of tumor cells) predicted reduced probability of tumor response to trastuzumab plus chemotherapy (multivariate odds ratio, 0.422; 95% confidence interval [CI], 0.222‐0.803; P = .009). In patients with hormone receptor‐positive tumors (≥1% of tumor cells), maintenance endocrine therapy added to trastuzumab upon the completion of chemotherapy was associated with a significant progression‐free survival benefit (hazard ratio, 0.521; 95% CI, 0.3325‐0.836; P = .007).

CONCLUSIONS:

Our results suggest a predictive role of hormone receptor expression in HER2‐positive tumors. Further investigation in this patient subset is warranted to optimize the use of HER2‐targeting agents, chemotherapy, and endocrine therapy. Cancer 2012;. © 2011 American Cancer Society.