bluuebunny/crossref_metadata_2025 huggingface dataset:
Cisplatin‐based combined modality therapy for anal carcinoma
Authors: Hung Arthur , Crane Christopher , Delclos Marc , Ballo Matthew , Ajani Jaffer , Lin Edward , Feig Barry , Skibber John , Janjan Nora
Published: February 2003

BACKGROUND

Definitive chemoradiation therapy is the standard of care for anal carcinoma. The chemotherapy regimen comprising 5‐fluorouracil (5‐FU) and mitomycin‐C is the most commonly used among patients with anal carcinoma but causes well documented toxicities. In the current study, the authors evaluated their experience in treating anal carcinoma with combined modality therapy using cisplatin and 5‐FU.

METHODS

A retrospective analysis was performed of 92 patients with nonmetastatic squamous cell carcinoma of the anus who were treated between 1989 and 1998. The primary tumor and involved lymph nodes received a total dose of 55 grays (Gy) administered in more than 30 daily fractions. Cisplatin (4 mg/m2/day) and 5‐FU (250 mg/m2/day) were given as a continuous infusion, 5 days each week during the entire radiation course. Kaplan–Meier methodology was used to determine local control (LC), disease‐free survival (DFS), and overall survival (OS).

RESULTS

Ten patients had T1 or Tx, 43 had T2, 27 had T3, and 12 patients had T4 disease. There were 21 male and 71 female patients. Sixty‐five patients (71%) were lymph node negative. With a median follow‐up duration of 44 months, the actuarial 5‐year OS rate was 85%, the DFS rate was 77%, and the colostomy‐free survival rate was 82%. Local recurrences occurred in 16 patients (17%). Distant metastases (DM) occurred in eight patients (9%). Advanced T classification (> T2) predicted lower LC and DFS rates. Advanced N classification (> N1) predicted worse DFS, OS, and DM rates. Greater than 90% of patients completed treatment without significant treatment interruption. Only five patients developed acute toxicities of Radiation Therapy Oncology Group (RTOG) Grade 4 or higher and only three patients developed chronic toxicities of RTOG Grade 4 or higher.

CONCLUSIONS

Combined modality therapy with continuous infusion of cisplatin and 5‐FU is a well tolerated regimen that results in high rates of LC, OS, and sphincter preservation. These rates are comparable to the best results reported with mitomycin‐C and 5‐FU. Without the normally severe toxicity, cisplatin‐based therapy results in a wider therapeutic index. Cancer 2003;97:1195–202. © 2003 American Cancer Society.

DOI 10.1002/cncr.11161
Extraskeletal myxoid chondrosarcoma
Authors: Kawaguchi Satoshi , Wada Takuro , Nagoya Satoshi , Ikeda Tatsuru , Isu Kazuo , Yamashiro Katsushige , Kawai Akira , Ishii Takeshi , Araki Nobuhito , Myoui Akira , Matsumoto Seiichi , Umeda Tohru , Yoshikawa Hideki , Hasegawa Tadashi
Published: February 2003

BACKGROUND

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment.

METHODS

Forty‐two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow‐up period was 7.4 years.

RESULTS

Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty‐three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease‐free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%.

CONCLUSIONS

These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy. Cancer 2003;97:1285–92. © 2003 American Cancer Society.

DOI 10.1002/cncr.11162
Author reply
Authors: Andea Aleodor A. , Wallis Tracie , Newman Lisa A. , Bouman David , Dey Jyotirmoy , Visscher Daniel W.
Published: February 2003

DOI 10.1002/cncr.11163
Oral pseudotumor
Authors: Oota Sayako , Shibuya Hitoshi , Hamagaki Miwako , Yoshimura Ryo‐ichi , Iwaki Hiroshi , Kojima Masaru , Takagi Minoru
Published: February 2003

BACKGROUND

The current study evaluated postirradiation pseudotumor in the oral cavity to investigate clinical and pathologic characteristics and incidence rates.

METHODS

Between 1960 and 1999, 2719 patients with squamous cell carcinoma of the oral cavity were treated with radiation therapy at Tokyo Medical and Dental University Hospital. Of these, six patients developed clinically polypoid tumors pathologically diagnosed as pseudotumors. Histopathology, immunohistology, and the clinical courses of these lesions were investigated.

RESULTS

Spindled fibroblastic cells arranged in whorled patterns were common pathologic features. Immunohistochemical results showed reactivity for vimentin and smooth muscle actin and nonreactivity for cytokeratin. The latent period from the initial radiation therapy to the development of the pseudotumor ranged from 45 to 145 months (median, 79 months). The overall cumulative incidence of pseudotumor was 0.22% during the 40 year period. All six patients were cured with simple excisions.

CONCLUSIONS

Oral carcinoma patients treated with radiation therapy may develop pseudotumor in a low frequency with a shorter period than that of radiation induced carcinoma/sarcoma. Pseudotumor was curable with surgery. Pseudotumor should be added to the list of differential diagnosis for postirradiation oral polypoid masses. Cancer 2003;97:1353–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11164
Intraoperative and conformal external‐beam radiation therapy with protracted 5‐fluorouracil infusion in patients with locally advanced pancreatic carcinoma
Authors: Furuse Junji , Kinoshita Taira , Kawashima Mitsuhiko , Ishii Hiroshi , Nagase Michitaka , Konishi Masaru , Nakagohri Toshio , Inoue Kazuto , Ogino Takashi , Ikeda Hiroshi , Maru Yasushi , Yoshino Masahiro
Published: February 2003

BACKGROUND

Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external‐beam radiaotherapy (EBRT), and protracted 5‐fluorouracil (5‐FU).

METHODS

Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5‐FU infusion (200 mg/m2), beginning 2–4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0–28.1 months. Survival from the date of IORT was calculated using the Kaplan–Meier method.

RESULTS

In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment‐related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2‐year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months.

CONCLUSIONS

The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5‐FU) for patients with locally advanced pancreatic carcinoma. Cancer 2003;97:1346–52. © 2003 American Cancer Society.

DOI 10.1002/cncr.11165
Second malignancies in children with neuroblastoma after combined treatment with 131I‐metaiodobenzylguanidine
Authors: Garaventa Alberto , Gambini Claudio , Villavecchia Giampiero , Di Cataldo Andrea , Bertolazzi Luigi , Pizzitola Maria Rosa , De Bernardi Bruno , Haupt Riccardo
Published: February 2003

BACKGROUND

131I‐metaiodobenzylguanidine (131I‐MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. Radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow‐up, other complications might occur. We describe our experience with second cancers occurring in children treated with 131I‐MIBG and chemotherapy.

METHODS

The clinical records of 119 consecutive NB cases treated with 131I‐MIBG at a single institution between 1984 and 2001 were reviewed for the occurrence of a second malignant neoplasm (SMN).

RESULTS

Overall, five cases of SMN occurred in the study patients. In particular, two cases of myeloid leukemia, one of angiomatous fibrous histiocytoma, one of malignant schwannoma, and one case of rhabdomyosarcoma were detected. The schwannoma and the rhabdomyosarcoma developed within the residual neuroblastic mass after first‐line therapy.

CONCLUSIONS

Should 131I‐MIBG treatment become more broadly employed in the therapeutic strategy for neuroblastoma, the risk of second cancer will have to be taken into consideration. The organization of an international registry of subjects treated with 131I‐MIBG might better define the frequency and features of second malignancies following this radiometabolic approach. Cancer 2003;97:1332–38. © 2003 American Cancer Society.

DOI 10.1002/cncr.11167
Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation
Authors: Komorizono Yasuji , Oketani Makoto , Sako Katsumi , Yamasaki Naruhiro , Shibatou Toshihiko , Maeda Masahiko , Kohara Kazunori , Shigenobu Shuhou , Ishibashi Kazuaki , Arima Terukatsu
Published: February 2003

BACKGROUND

The objectives of this study were to clarify risk factors for local tumor recurrence and to determine which patients with hepatocellular carcinoma (HCC) are most suitable for a single session, single application of percutaneous radiofrequency (RF) ablation.

METHODS

Fifty‐six consecutive patients with 65 HCC tumors measuring ≤ 3 cm in greatest dimension who received a single session, single application of percutaneous RF ablation and who achieved optimal tumor ablation, as assessed by an immediate computed tomography scan, were enrolled in this study. Six possible factors for local recurrence were analyzed using a Cox proportional hazards regression model: tumor size, tumor location, proximity of the tumor to intrahepatic large vessels, types of electrodes used, prior treatment, and observation of impedance rises. Local recurrence free intervals were estimated using the Kaplan–Meier method, and differences between groups were compared using the log‐rank test.

RESULTS

The Kaplan–Meier estimates of overall cumulative local recurrence free intervals after a single RF ablation treatment were 76% (95% confidence interval [95%CI], 70.9–81.7%) at 12 months and 74% (95%CI, 68.2–79.6%) at 15 months. The log‐rank test revealed a statistically significant difference between the local recurrence free intervals according to tumor size (P = 0.001) and tumor location (P < 0.001). Further investigation with a Cox regression analysis indicated that a greatest tumor dimension > 2 cm (risk ratio [RR], 4.9; 95%CI, 1.3–16.4; P = 0.019) and subcapsular location (RR, 5.2; 95%CI, 1.7–16.6; P = 0.005) were associated independently with local recurrence. The other four factors were not associated with local recurrence in this study.

CONCLUSIONS

A single session, single application of RF ablation produced favorable local control. Patients who have nonsubcapsular HCC tumors measuring ≤ 2 cm in greatest dimension may be the most suitable candidates for a single‐session, single application of RF ablation. Cancer 2003;97:1253–62. © 2003 American Cancer Society.

DOI 10.1002/cncr.11168
Mammography screening among Chinese‐American women
Authors: Tu Shin‐Ping , Yasui Yutaka , Kuniyuki Alan A. , Schwartz Stephen M. , Jackson J. Carey , Hislop Thomas Gregory , Taylor Vicky
Published: February 2003

BACKGROUND

Breast carcinoma is the most common major malignancy among several Asian‐American populations. This study surveyed mammography screening knowledge and practices among Chinese‐American women.

METHODS

In 1999, the authors conducted a cross‐sectional, community‐based survey in Seattle, Washington. Bilingual and bicultural interviewers administered surveys in Mandarin, Cantonese, or English at participants' homes.

RESULTS

The survey cooperation rate (responses among reachable and eligible households) was 72% with 350 eligible women (age ≥ 40 years with no prior history of breast carcinoma or double mastectomy). Seventy‐four percent of women reported prior mammography screening, and 61% of women reported screening in the last 2 years. In multivariate analysis, a strong association was found between mammography screening and recommendations by physicians and nurses (prior screening: odds ratio [OR], 16.0; 95% confidence interval [95% CI], 7.8–35.0; recent screening: OR, 7.0; 95% CI, 3.8–13.6). This finding applied to both recent immigrants (< 15 years in the U.S.) and earlier immigrants (≥ 15 years in the U.S.). Thirty‐two percent of women reported that the best way to detect breast carcinoma was a modality other than mammogram.

CONCLUSIONS

The authors recommend a multifaceted approach to increase mammography screening by Chinese‐American women: recommendations from the provider plus targeted education to address the effectiveness of screening mammography compared with breast self examination and clinical breast examination. Cancer 2003;97:1293–302. © 2003 American Cancer Society.

DOI 10.1002/cncr.11169
Refined measurement of outcome for adjuvant breast carcinoma therapy
Authors: Gamel John W. , Bonadonna Gianni , Valagussa Pinuccia , Edwards Michael J.
Published: February 2003

BACKGROUND

Traditional nonparametric statistical methods do not provide a quantitative measure of the lifetime benefit from adjuvant therapy. This deficiency makes it difficult to determine the long‐term difference in impact between the two treatment arms of a clinical trial.

METHODS

To assess the impact of breast carcinoma recurrence, parametric survival models were derived from two randomized, controlled clinical trials of adjuvant therapy for Stage II breast carcinoma. To assess time to death from causes other than breast carcinoma, actuarial models derived from 1980 Census data were used. These two models were then combined to estimate the mean time to event (MTE) as a function of patient age, with the event being either recurrence or death from other causes. The MTE was then used to measure the differential benefit between two arms of a clinical trial.

RESULTS

In the first trial, differences in MTE between treatment groups varied from 2.7 years for 35‐year‐old patients to 1.4 years for 75‐year‐old patients. For this trial, the mechanism of survival benefit was an increase in time to recurrence. In the second trial, differences in MTE varied from 7.6 to 1.6 years over the same age ranges. For this trial, the mechanism of survival benefit was an increase in the likelihood of cure, i.e., an increase in the asymptote of the curve that represents proportion of patients without relapse.

CONCLUSIONS

When applied to data from controlled clinical trials, MTE offers a quantitative measure of long‐term outcome from adjuvant therapy. The greatest benefit is achieved when therapy that increases the likelihood of cure is provided to young patients. Cancer 2003;97:1139–46. © 2003 American Cancer Society.

DOI 10.1002/cncr.11171
5‐Year mammography rates and associated factors for older women
Authors: Van Harrison R. , Janz Nancy K. , Wolfe Robert A. , Tedeschi Philip J. , Huang Xuelin , McMahon Laurence F.
Published: February 2003

BACKGROUND

Major national interventions occurred in the early and mid‐1990s to increase mammography screening rates among older women. The current study examined mammography utilization by older women during this period. Relation between mammography utilization and demographic measures and health care‐related factors also were examined.

METHODS

A cross‐sectional design examined variations in mammography during the 5 years between 1993 to 1997 in a representative sample of 10,000 female Medicare beneficiaries in Michigan age ≥ 65 years in 1993. Medicare and census data were used. Separate analyses were performed for having undergone any mammogram and, for the 5680 women who had undergone a mammogram, the number of mammograms. Relations were examined between mammography utilization and 15 demographic variables (e.g., age and African‐American race) and health care‐related variables (e.g., inpatient admissions and number of physicians involved in care).

RESULTS

In the 5 years 43% of older women had no evidence of having undergone a mammogram. Those with any mammogram averaged 2.8 mammograms. Meaningful independent predictors of both having undergone a mammogram and having more than one mammogram were more physicians involved in care, fewer inpatient admissions, and younger age. Having undergone a mammogram also was found to be associated with seeing an obstetrician/gynecologist.

CONCLUSIONS

Even with screening mammography as a covered benefit and after several national informational campaigns, the current study found that in 5 years, 60% of older women either had not undergone a mammogram or had undergone only 1. Intervention efforts should emphasize screening based on functional status, not age. This message should be targeted to physicians as well as to older women without claims for recent mammograms and who are likely to be in good health. Cancer 2003;97:1147–55. © 2003 American Cancer Society.

DOI 10.1002/cncr.11172
Is axillary lymph node dissection necessary in elderly patients with breast carcinoma who have a clinically uninvolved axilla?
Authors: Martelli Gabriele , Miceli Rosalba , De Palo Giuseppe , Coradini Danila , Salvadori Bruno , Zucali Roberto , Galante Emanuele , Marubini Ettore
Published: February 2003

BACKGROUND

Axillary dissection in elderly patients with early‐stage breast carcinoma who do not have palpable axillary lymph nodes is controversial because of the associated morbidity of the surgery, reduced life expectancy of the patients, and efficacy of hormone therapy in preventing recurrences and axillary events.

METHODS

The authors performed a retrospective analysis of 671 consecutive patients with breast carcinoma who were age ≥ 70 years and who underwent conservative breast surgery with axillary dissection (172 patients) or without axillary dissection (499 patients). Tamoxifen always was given. The effects of axillary dissection compared with no axillary dissection on breast carcinoma mortality and distant metastasis were analyzed using multiple proportional‐hazards regression models. Because the assignment to axillary treatment was nonrandom, covariate adjustments were made for baseline variables that influenced the decision to perform axillary dissection and for prognostic factors.

RESULTS

The crude cumulative incidence curves for breast carcinoma mortality and distant metastasis did not appear to differ significantly between the two groups (P = 0.530 and P = 0.840, respectively). The crude cumulative incidences of axillary lymph node occurrence at 5 years and 10 years were 4.4% and 5.9%, respectively (3.1% and 4.1%, respectively, for patients with pT1 tumors).

CONCLUSIONS

Elderly patients with breast carcinoma who have no evidence of axillary lymph node involvement may be treated effectively with conservative surgery and tamoxifen. Immediate axillary dissection is not necessary but should be performed in the small percentage of patients who later develop overt axillary lymph node involvement. Cancer 2003;97:1156–63. © 2003 American Cancer Society.

DOI 10.1002/cncr.11173
Evaluation of an internet support group for women with primary breast cancer
Authors: Winzelberg Andrew J. , Classen Catherine , Alpers Georg W. , Roberts Heidi , Koopman Cheryl , Adams Robert E. , Ernst Heidemarie , Dev Parvati , Taylor C. Barr
Published: February 2003

BACKGROUND

Women with breast carcinoma commonly experience psychologic distress following their diagnosis. Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives. Web‐based breast cancer social support groups are widely used, but little is known of their effectiveness. Preliminary evidence suggests that women benefit from their participation in web‐based support groups.

METHODS

Seventy‐two women with primary breast carcinoma were assigned randomly to a 12‐week, web‐based, social support group (Bosom Buddies). The group was semistructured, moderated by a health care professional, and delivered in an asynchronous newsgroup format.

RESULTS

The results indicate that a web‐based support group can be useful in reducing depression and cancer‐related trauma, as well as perceived stress, among women with primary breast carcinoma. The effect sizes ranged from 0.38 to 0.54. Participants perceived a variety of benefits and high satisfaction from their participation in the intervention

CONCLUSIONS

This study demonstrated that the web‐based program, Bosom Buddies, was effective in reducing participants' scores on depression, perceived stress, and cancer‐related trauma measures. The effect size of the intervention was in the moderate range. Although web‐based social support groups offer many advantages, this delivery mechanism presents a number of ethical issues that need to be addressed. Cancer 2003;97:1164–73. © 2003 American Cancer Society.

DOI 10.1002/cncr.11174
Pure versus follicular variant of papillary thyroid carcinoma
Authors: Zidan Jamal , Karen Drumea , Stein Moshe , Rosenblatt Edward , Basher Walid , Kuten Abraham
Published: February 2003

BACKGROUND

The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival.

METHODS

A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty‐three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival.

RESULTS

The median follow‐up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21‐year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant).

CONCLUSIONS

The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Cancer 2003;97:1181–5. © 2003 American Cancer Society.

DOI 10.1002/cncr.11175
Impact of a novel neoadjuvant and adjuvant hormone‐deprivation approach on quality of life, voiding function, and sexual function after prostate brachytherapy
Authors: Miller Nicole L. , Bissonette Eric A. , Bahnson Robert , Wilson John , Theodorescu Dan
Published: February 2003

BACKGROUND

Data demonstrate a benefit from neoadjuvant and adjuvant hormone‐deprivation therapy with luteinizing hormone‐releasing hormone agonists in patients who are treated with radiotherapy for localized prostate carcinoma; however, this approach has detrimental effects on quality of life (QOL). A cross‐sectional study was undertaken to evaluate the impact on QOL, voiding function, and sexual function of an alternative hormone‐deprivation approach.

METHODS

Three hundred fifty patients with clinical T1c–T2b prostate carcinoma were treated from March 1997 to August 2000 either with palladium 103 brachytherapy (BTM) without hormone therapy or with 8 months of adjuvant and neoadjuvant hormone‐deprivation therapy with an antiandrogen and finasteride (BTM+H), were mailed the Functional Assessment of Cancer Therapy (FACT) global well being QOL instrument (FACT‐G), the American Urological Association symptom score (AUASS), and specific items addressing urinary control and sexual function from validated instruments. Differences between treatment groups were assessed as a function of time since treatment.

RESULTS

Seventy‐two percent of patients responded to the questionnaire. No differences in overall FACT‐G scores, AUASS scores, or AUASS subscale scores between the BTM group and the BTM+H group were found. The BTM+H group initially had lower personal well being FACT‐G subscale scores, more urinary incontinence, and lower odds of attaining an erection sufficient for intercourse initially, although these differences disappeared with longer follow‐up.

CONCLUSIONS

The use of neoadjuvant and adjuvant antiandrogen and finasteride with brachytherapy is associated with QOL equal to that of brachytherapy alone for the treatment of patients with localized prostate carcinoma, allowing the advantages of hormone manipulation in terms of tumor control without its downside. Cancer 2003;97:1203–10. © 2003 American Cancer Society.

DOI 10.1002/cncr.11177
Elevation of cytokine levels in cachectic patients with prostate carcinoma
Authors: Pfitzenmaier Jesco , Vessella Robert , Higano Celestia S. , Noteboom Jennifer L. , Wallace David , Corey Eva
Published: February 2003

BACKGROUND

Approximately 60–70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor α (TNFα) and interleukin 1 (IL‐1), IL‐6, and IL‐8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFα, IL‐1β, IL‐6, and IL‐8.

METHODS

The levels of TNFα, IL‐1β, IL‐6, IL‐8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ‐confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total‐PSA assays were used to determine cytokine and PSA levels, respectively.

RESULTS

Levels of TNFα, IL‐6, and IL‐8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFα were correlated positively with IL‐8, and there was no correlation between PSA levels and any of the cytokine levels. IL‐1β levels were below the limit of detection in all samples.

CONCLUSIONS

The current results show that levels of TNFα, IL‐6, and IL‐8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia. Cancer 2003;97:1211–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11178
High‐dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma
Authors: Beer Tomasz M. , Lemmon Dianne , Lowe Bruce A. , Henner W. David
Published: February 2003

BACKGROUND

In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long‐term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone‐naïve prostate carcinoma.

METHODS

Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 μg/kg orally once each week until a maximum of a four‐fold increase in the PSA.

RESULTS

Twenty‐two patients received treatment for a median of 10 months (range, 2–25+ months). Treatment was well tolerated with no Grade ≥ 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50% reduction confirmed 4 weeks later). Three patients (14%, 95% CI 0–28%) had confirmed reductions in the PSA ranging from 10% to 47%. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test).

CONCLUSIONS

Weekly high‐dose calcitriol was found to be safe. The primary efficacy endpoint of 50% reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression. Cancer 2003;97:1217–24. © 2003 American Cancer Society.

DOI 10.1002/cncr.11179
A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome
Authors: Cortes Jorge , Kantarjian Hagop , Albitar Maher , Thomas Deborah , Faderl Stefan , Koller Charles , Garcia‐Manero Guillermo , Giles Francis , Andreeff Michael , O'Brien Susan , Keating Michael , Estey Elihu
Published: February 2003

BACKGROUND

Because angiogenesis may play a role in the pathogenesis of acute myeloid leukemia (AML) and high‐risk myelodysplastic syndrome (MDS), and thalidomide (Th) has shown significant anti‐angiogenic activity, this study was designed to investigate the potential role of Th in the treatment of patients with AML and MDS and the possible role of a non–ara‐C‐containing regimen.

METHODS

Adults with AML or high‐risk MDS and cytogenetic abnormalities other than inv (16), t(8;21), ‐Y or ‐X were randomized to receive liposomal daunorubicin (DNX) and ara‐C (DA) or DNX and topotecan (DT). Within each arm, patients were randomized to receive chemotherapy alone (DA or DT) or with thalidomide (DATh or DTTh). Vascular endothelial growth factor (VEGF) plasma levels and microvascular density was measured before and after therapy. Eighty‐four patients (median age, 65 years; range, 27–84 years) were treated.

RESULTS

None of 11 patients treated with DT or DTTh responded and these arms were closed. Seventeen of 37 patients treated with DA and 15 of 36 treated with DATh achieved an early complete remission. Median complete response duration was 38 and 34 weeks (P = 0.57) and median survival 35 and 28 weeks (P = 0.15), respectively. Patients with high pretreatment VEGF levels had an inferior survival. There was no significant difference in the changes in VEGF levels or microvascular density after treatment in patients who did versus those who did not receive thalidomide.

CONCLUSIONS

The authors concluded that thalidomide in combination with chemotherapy does not result in clinical benefit in patients with AML or high‐risk MDS. Cancer 2003;97:1234–41. © 2003 American Cancer Society.

DOI 10.1002/cncr.11180
Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma
Authors: Sobin Leslie H. , Greene Frederick L.
Published: February 2003

DOI 10.1002/cncr.11182
Chromosomal aberrations of primary lung adenocarcinomas in nonsmokers
Authors: Wong Maria P. , Fung Lai‐Fan , Wang Elaine , Chow Wing‐Shun , Chiu Shui‐Wah , Lam Wah‐Kit , Ho Kwok‐Keung , Ma Edmond S. K. , Wan Thomas S. K. , Chung Lap‐Ping
Published: February 2003

BACKGROUND

Lung carcinoma is a common malignancy, and tobacco carcinogenesis is the major cause. Studies on individual genes or loci have suggested, that in tumors from nonsmokers, different genetic alterations are present compared with tumors from smokers. It is possible that distinct genetic pathways may be involved. However, the targets remain largely unknown; and, to the authors' knowledge, molecular cytogenetics studies on lung carcinomas from nonsmokers have not been reported.

METHODS

Comparative genomic hybridization (CGH) analysis was performed on primary lung adenocarcinoma samples from 32 patients who never smoked to identify loci of frequent aberrations.

RESULTS

Different extents of aberration were found in 31 of the 32 samples studied. The most frequently altered locus was gain of 16p (59% of samples) followed by gain of 20q (44% of samples), with the minimal overlapping regions at 16p13.1‐p13.2 and 20q13.2, respectively. Other over‐represented loci with > 30% frequency were observed at 5p (34% of samples), 7p (41% of samples), 8q (31% of samples), 17q (34% of samples), and 19q (34% of samples); and high‐level DNA amplifications were detected at 1q, 7p, 12q, 19q, and 20q. DNA under‐representation was observed less commonly and included 8p (28% of samples), 9p (22% of samples), 13q (28% of samples), and 18q (38% of samples).

CONCLUSIONS

The current study identified targets of frequent genetic aberration in primary adenocarcinomas from nonsmokers. Compared with reported CGH findings in the literature, the current findings suggest that DNA gain at 16p is the distinct aberration involved in these tumors. Other frequently altered loci involve commonly reported oncogenic and tumor suppressor loci, suggesting an overlap with the genetic pathways of tobacco‐induced lung carcinogenesis. Cancer 2003;97:1263–70. © 2003 American Cancer Society.

DOI 10.1002/cncr.11183
Long‐term follow‐up of a phase I study of high‐dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias
Authors: de Lima Marcos , Ravandi Farhad , Shahjahan Munir , Andersson Borje , Couriel Daniel , Donato Michele , Khouri Issa , Gajewski James , van Besien Koen , Champlin Richard , Giralt Sergio , Kantarjian Hagop
Published: February 2003

BACKGROUND

Decitabine is a hypomethylating agent that has activity in patients with leukemia. The authors combined decitabine with busulfan and cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation.

METHODS

Patients with high‐risk acute myeloid leukemia (AML) (n = 12 patients); chronic myelomonocytic leukemia (CMML) (n = 1 patient); acute lymphocytic leukemia (ALL) (n = 1 patient); or late chronic phase, accelerated, or blastic phase chronic myelogenous leukemia (n = 9 patients) were eligible for the study. The treatment plan was comprised of busulfan, 12 mg/kg orally; cyclophosphamide, 100 mg/kg (n = 4 patients) or 120 mg/kg (n = 19 patients); and decitabine, intravenously at 3 dose levels: 400 mg/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (n = 5 patients). Donors were human leukocyte antigen‐identical siblings in all cases, and all but one patient received peripheral blood stem cells. Graft‐versus‐host disease (GVHD) prophylaxis was tacrolimus based in all but one patient.

RESULTS

The median time to neutrophil and platelet engraftment was 12.5 days and 17.5 days, respectively. Twenty‐one patients were engrafted and achieved disease remission. At a median of 3.3 years posttransplantation, 26% of patients (40% of patients with AML) were alive and disease free. The median survival for the group was 17.2 months, and the disease free survival for the group was 8.9 months. Causes of death were disease recurrence (nine patients), chronic GVHD (four patients), infections (three patients), and acute GVHD (one patient). The 100‐day mortality rate was 9%. No decitabine dose‐limiting toxicity was documented. The treatment‐related mortality rate at 3 years was 35%. Responders were treated at all three decitabine dose levels, and no dose‐response correlation was observed.

CONCLUSIONS

There was a high response rate with low treatment‐related mortality, with 26% of patients alive in remission 3.3 years after transplantation. Cancer 2003;97:1242–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11184
Overdiagnosis in chest radiographic screening for lung carcinoma
Authors: Yankelevitz David F. , Kostis William J. , Henschke Claudia I. , Heelan Robert T. , Libby Daniel M. , Pasmantier Mark W. , Smith James P.
Published: February 2003

BACKGROUND

The pattern of results in the Mayo Lung Project (MLP), which is the basis for the prevailing recommendations against radiographic screening for lung carcinoma, has led to the assertion that up to 50% of the diagnosed cases of early‐stage disease in that trial may have represented overdiagnosed, indolent cases. This finding suggests the possibility of such a high frequency of overdiagnosis in chest radiographic lung carcinoma screening in general. In the current study, the authors analyzed data from the MLP and its counterpart study at Memorial Sloan‐Kettering Cancer Center (MSK) to estimate the frequency of overdiagnosis in these studies.

METHODS

For the cases diagnosed as Stage I in the MLP and the MSK studies, the doubling times of tumor volumes were calculated. The calculations were based on size measurements recorded by the original investigators from chest radiographs taken during the course of each study.

RESULTS

The median doubling times were 101 days in the MLP and 144 days in the MSK, times that are somewhat shorter than those reported in published series of adenocarcinoma cases diagnosed outside screening, and only 5% had doubling times exceeding 400 days.

CONCLUSIONS

The hypothesis that early‐stage lung tumors diagnosed on chest radiography during lung carcinoma screening may frequently be overdiagnosed, indolent cases needs to be rejected. Cancer 2003;97:1271–5. © 2003 American Cancer Society.

DOI 10.1002/cncr.11185
A randomized, active‐control, pilot trial of front‐loaded dosing regimens of darbepoetin‐alfa for the treatment of patients with anemia during chemotherapy for malignant disease
Authors: Glaspy John A. , Jadeja Jaswant Sinh , Justice Glen , Fleishman Alex , Rossi Gregory , Colowick Alan B.
Published: February 2003

BACKGROUND

Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin α, a new erythropoietic agent, has longer serum residence time, allowing it to be administered less frequently.

METHODS

Patients (n = 127) were randomized to receive study drug for 12 weeks: either rHuEPO 40,000 U with escalations to 60,000 U for nonresponders or darbepoetin α at doses of 4.5 μg/kg per week until hemoglobin concentration ≥ 12 g/dL, then 1.5 μg/kg per week (Group 1); 4.5 μg/kg per week for 4 weeks, then 2.25 μg/kg per week for 8 weeks (Group 2); or 4.5 μg/kg per week for 4 weeks, then 3.0 μg/kg every 2 weeks (Group 3). Efficacy was measured using the mean change in hemoglobin level, the proportion of patients achieving a hemoglobin response, the time to response, and the mean change in Functional Assessment of Cancer Therapy‐Fatigue Scale scores. Safety was assessed by reports of adverse events.

RESULTS

Overall, after 4 weeks of treatment, the mean change (95% confidence interval [95%CI]) in hemoglobin concentration was 0.53 g/dL (95%CI, 0.05–1.02 g/dL), 0.70 g/dL (95%CI, 0.11–1.29 g/dL), and 0.90 g/dL (95%CI, 0.47–1.33 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 0.39 g/dL (95%CI, − 0.22–1.00 g/dL) in the rHuEPO group. By the end of the study, the mean change (95%CI) in hemoglobin concentration was 1.35 g/dL (95%CI, 0.67–2.02 g/dL), 1.35 g/dL (95%CI, 0.57–2.12 g/dL), and 1.28 g/dL (95%CI, 0.84–1.73 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 1.03 g/dL (95%CI, 0.53–1.53 g/dL) in the rHuEPO group. The early erythropoietic response in patients who were treated with darbepoetin α was associated with an early and maintained reduction in patient‐reported fatigue. The adverse event profile was comparable with all doses of darbepoetin α and rHuEPO.

CONCLUSIONS

Darbepoetin α, given as a front‐loaded dose for 4 weeks and followed by lower and/or less frequent doses, appears to be efficacious and may decrease the time to response relative to treatment with rHuEPO. Cancer 2003;97:1312–20. © 2003 American Cancer Society.

DOI 10.1002/cncr.11186
Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features
Authors: van den Bent Martin J. , Looijenga Leendert H. J. , Langenberg K. , Dinjens Winand , Graveland Wilfried , Uytdewilligen Ludo , Sillevis Smitt Peter A. , Jenkins Robert B. , Kros Johan M.
Published: February 2003

BACKGROUND

Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy.

METHODS

The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction–single‐strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB‐1 antibody.

RESULTS

Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low‐grade tumors that manifested with seizures of long‐standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q.

CONCLUSIONS

OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low‐grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276–84. © 2003 American Cancer Society.

DOI 10.1002/cncr.11187
Ki‐67 expression in breast carcinoma
Authors: Trihia Helen , Murray Susan , Price Karen , Gelber Richard D. , Golouh Rastko , Goldhirsch Aron , Coates Alan S. , Collins John , Castiglione‐Gertsch Monica , Gusterson Barry A.
Published: February 2003

BACKGROUND

The number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki‐67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine‐needle aspirates and small biopsies.

METHODS

Immunohistochemistry using the anti‐Ki‐67 antibody MIB‐1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki‐67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki‐67 grade (NKG) and to assess Ki‐67 as a single parameter.

RESULTS

In both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki‐67 group was correlated significantly with Bloom–Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c‐erbB‐2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki‐67 percentage was correlated significantly with c‐erbB‐2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki‐67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group.

CONCLUSIONS

Ki‐67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki‐67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine‐needle aspirates. Cancer 2003;97:1321–31. © 2003 American Cancer Society.

DOI 10.1002/cncr.11188