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Skye Hung-Chun Cheng,
Stella Y Tsai,
Ben-Long Yu,
Cheng-Fang Horng,
Chii-Ming Chen,
James J Jian,
Nan-Min Chu,
Mei-Hua Tsou, Mei-Ching Liu,
Andrew T Huang,
Leonard R Prosnitz
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ABSTRACT: PURPOSE: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. RESULTS: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. CONCLUSIONS: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.
International journal of radiation oncology, biology, physics 11/2012; · 4.59 Impact Factor
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Luca Gianni,
Tadeusz Pienkowski,
Young-Hyuck Im,
Laslo Roman,
Ling-Ming Tseng, Mei-Ching Liu,
Ana Lluch,
Elżbieta Staroslawska,
Juan de la Haba-Rodriguez,
Seock-Ah Im,
Jose Luiz Pedrini,
Brigitte Poirier,
Paolo Morandi,
Vladimir Semiglazov,
Vichien Srimuninnimit,
Giulia Bianchi,
Tania Szado,
Jayantha Ratnayake,
Graham Ross,
Pinuccia Valagussa
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ABSTRACT: Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting.
In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2), escalating, if tolerated, to 100 mg/m(2) every 3 weeks; group A) or pertuzumab (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint, examined in the intention-to-treat population, was pathological complete response in the breast. Neither patients nor investigators were masked to treatment. This study is registered with ClinicalTrials.gov, number NCT00545688.
Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate (49 of 107 patients; 45·8% [95% CI 36·1-55·7]) compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29·0% [20·6-38·5]; p=0·0141). 23 of 96 (24·0% [15·8-33·7]) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16·8% [10·3-25·3]) given pertuzumab and trastuzumab (group C). The most common adverse events of grade 3 or higher were neutropenia (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52 of 94 in group D), febrile neutropenia (eight, nine, none, and seven, respectively), and leucopenia (13, five, none, and seven, respectively). The number of serious adverse events was similar in groups A, B, and D (15-20 serious adverse events per group in 10-17% of patients) but lower in group C (four serious adverse events in 4% of patients).
Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer.
F Hoffmann-La Roche.
The lancet oncology 12/2011; 13(1):25-32. · 14.47 Impact Factor
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Dennis Slamon,
Wolfgang Eiermann,
Nicholas Robert,
Tadeusz Pienkowski,
Miguel Martin,
Michael Press,
John Mackey,
John Glaspy,
Arlene Chan,
Marek Pawlicki, [......],
Guido Sauter,
Gunter von Minckwitz,
Frances Visco,
Valerie Bee,
Marc Buyse,
Belguendouz Bendahmane,
Isabelle Tabah-Fisch,
Mary-Ann Lindsay,
Alessandro Riva,
John Crown
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ABSTRACT: Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.
We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.
At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.
The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).
New England Journal of Medicine 10/2011; 365(14):1273-83. · 53.30 Impact Factor
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ABSTRACT: The purpose of this study is to evaluate the performance of gallium-67 scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and recurrence detection by comparing the 2 imaging studies in the same patient.
A total of 42 patients from the period between July 2002 and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG PET scans and also underwent corresponding GS performed within 7 days of FDG PET, for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed in these 42 patients, 27 were for staging, and 19 for restaging after recurrence.
In all these studies, FDG PET detected 230 lesion sites, whereas GS detected 85 lesion sites. All of the lesions detected by GS were noted on FDG PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the 27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68 lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110 lesions, whereas GS detected only 17 (15.5%).
FDG PET is superior to GS in staging and detecting all types of lymphoma. The difference is notably more significant in recurrence detection.
Clinical nuclear medicine 10/2011; 36(10):867-71. · 3.92 Impact Factor
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ABSTRACT: The laparoscopic approach has played a key role in the successful application of the enhanced recovery program (ERP) in perioperative care for postoperative colon surgery patients. Reports of applying ERP in laparoscopic rectal surgery are rare, and the feasibility of doing so has yet to be solidly evaluated. The goal of this study was to evaluate whether it is appropriate to use ERP on patients who undergo rectal surgery via the laparoscopic approach and to further investigate potential factors that may affect the results of this practice modality.
Between December 2007 and July 2009, 80 eligible patients (35 women) with a median age of 60 (range, 28-82) years were enrolled. All patients received elective laparoscopic rectal surgery due to malignant or benign rectal lesions. Forty-nine percent of patients received preoperative neoadjuvant chemoradiotherapy (CCRT), because their clinical stage was beyond T3N0 or TanyN(+). The ERP used in this study was modified from a similar protocol used for patients receiving laparoscopic colectomy at the same institution.
Sixty-five percent of patients in the study received a sphincter-preserving procedure, whereas 15 other patients underwent abdominoperineal resection (APR). The median operative time was 160 min. The conversion rate of laparoscopic surgery was 7.5%, and the combined intraoperative and postoperative complication rate was 13.8%. Forty-two patients (52.5% of the study pool) received complete postoperative recovery courses as prescribed by ERP.
Our preliminary results of applying ERP to patients receiving laparoscopic rectal surgery showed a success rate of 52.5%. The failure of ERP among these patients was related to low rectal lesion locations (below 7 cm AAV) and surgery-related complications. ERP for laparoscopic rectal surgery is feasible but is not advised for all cases requiring laparoscopic rectal surgery.
Surgical Endoscopy 10/2010; 25(5):1477-83. · 4.01 Impact Factor
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Carlos H Barrios, Mei-Ching Liu,
Soo Chin Lee,
Laurence Vanlemmens,
Jean-Marc Ferrero,
Toshio Tabei,
Xavier Pivot,
Hiroji Iwata,
Kenjiro Aogi,
Roberto Lugo-Quintana,
Nadia Harbeck,
Marla J Brickman,
Ke Zhang,
Kenneth A Kern,
Miguel Martin
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ABSTRACT: This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m(2) (1,000 mg/m(2) in patients >65 years) BID on days 1-14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16-1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.
Breast Cancer Research and Treatment 03/2010; 121(1):121-31. · 4.43 Impact Factor
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ABSTRACT: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1).
Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups.
With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%.
Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.
International journal of radiation oncology, biology, physics 08/2009; 77(2):516-22. · 4.59 Impact Factor
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ABSTRACT: International initiatives increasingly advocate physician adherence to clinical protocols that have been shown to improve outcomes, yet the process-outcome relationship for adhering to breast cancer care protocol is unknown.
This study explores whether 100% adherence to a set of quality indicators applied to individuals with breast cancer is associated with better survival.
Ten quality indicators (4 diagnosis-related and 6 treatment-related indicators) were used to measure the quality of care in 1378 breast cancer patients treated from 1995 to 2001. Adherence to each indicator was based on the number of procedures performed divided by the number of patients eligible for that procedure. The main analysis of adherence was dichotomous (ie, 100% adherence vs. <100% adherence).
The outcome measures studied were 5-year overall survival and progression-free survival, calculated using the Kaplan-Meier method. The Cox's proportional hazard regression model was used for univariate and multivariate analyses.
Most patients received care that demonstrated good adherence to the quality indicators. Multivariate analysis revealed that 100% adherence to entire set of quality indicators was significantly associated with better overall survival [hazard ratio (HR): 0.46; 95% confidence interval (CI): 0.33-0.63] and progression-free survival (HR 0.51; 95% CI, 0.39-0.67). One hundred percent adherence to treatment indicators alone was also associated with statistically significant improvements in overall and progression-free survivals.
Our study strongly supports that 100% adherence to evidence supported quality-of-care indicators is associated with better survival rates for breast cancer patients and should be a priority for practitioners.
Medical care 02/2009; 47(2):217-25. · 3.24 Impact Factor
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ABSTRACT: Neoadjuvant chemoradiation therapy has improved the local control rate and overall survival in locally advanced rectal cancers. The purpose of this retrospective study is to evaluate the correlation between the final pathologic stage and survival in these patients.
Patients with biopsy-proven rectal carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4 tumors, or node-positive disease were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed by radical surgical resection. Clinical outcome with survival, disease-free survival, recurrence rate, and local recurrence rate were compared with each T and N findings using the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging system.
A total of 248 patients were enrolled in this study. Overall survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9% and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a pathologic complete response after neoadjuvant therapy. The recurrence rate was significantly different between the pathologic complete response group and residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was significantly better in the complete response group than the residual tumor group (93 vs 66%; P = .0045). There was no statistical difference in survival or locoregional recurrence rate between these two groups.
Posttreatment pathologic TNM stage is correlated to disease-free survival and tumor recurrence rate in locally advanced rectal cancer after preoperative chemoradiation. Also, pathologic complete response to neoadjuvant treatment has its oncologic benefit in both overall recurrence and disease-free survival.
Annals of Surgical Oncology 11/2007; 14(10):2766-72. · 4.17 Impact Factor
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ABSTRACT: The clinicopathological characteristics of malignant lymphomas vary according to geography. The purpose of this study is to determine the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan. Archival tissue from 598 malignant lymphomas during the period of 1995-2002 was retrieved. They were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. There were 330 males and 268 females. The median age at onset of disease was 56 years for B-cell lymphoma (BCL), 50 years for T/NK-cell lymphoma (TCL), and 26 years for Hodgkin's lymphoma (HL). BCL accounted for 80.6%, TCL for 12.4%, and HL for 7%. The major subtypes of non-HL were diffuse large B-cell lymphoma, follicular lymphoma, plasma cell myeloma, marginal zone lymphoma of mucosa-associated lymphoid tissue type, mantle cell lymphoma, unspecified peripheral TCL, and nasal type T/NK-cell lymphoma. Nodular sclerosing subtype was the most common in HL. The frequencies of TCL and HL were relatively low. For histological subtype, enteropathy-type TCL and primary bone marrow HL had higher frequency and poorer prognosis. The 5-year overall survival of BCL, TCL, and HL was 58.9, 34.7, and 83.5%, respectively. To the best of our knowledge, this is the largest series study of malignant lymphoma in Taiwan. Immunophenotype, histological subtype, and clinical stage play significant roles in prognosis (P < 0.05).
American Journal of Hematology 09/2006; 81(8):568-75. · 4.67 Impact Factor
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ABSTRACT: Pleural fluid loculations or trapped lungs frequently render patients with symptomatic malignant pleural effusions (MPEs) unsuitable for pleurodesis. Thoracoscopic surgery or thoracotomy with decortication is generally not feasible for patients with a poor performance status. MPEs have augmented procoagulant and depressed fibrinolytic activity that contributes to fibrin deposition within the pleural space. The authors conducted an observational prospective cohort study to investigate the use of intrapleural urokinase (IPUK) for such patients and made a comparison with a historical control group.
Between March of 2000 and August of 2005, 48 consecutive patients with symptomatic MPEs with an average Karnofsky performance scale score of 46.7% were recruited. Dyspnea persisted with the presence of substantial residual loculated MPEs in 36 patients and trapped lungs in 12 patients, when the effectiveness of 8-French intrapleural catheter drainage had decreased despite regular saline flushes. Urokinase was instilled daily through the catheter at a dose of 100,000 IU diluted in 100 ml of normal saline for 3 days. Additional IPUK instillation was required upon partial improvement. The records and chest radiographs of another 52 patients with symptomatic MPEs had met these eligibility criteria between January of 1995 and February of 2000 and received saline flushes only were also reviewed.
Immediate lung reexpansion and resolution of dyspnea was achieved in 29 of the 48 patients who underwent IPUK therapy (60.4%). The mean dose of urokinase instillations per patient was 360,000 IU. There were no major complications. A significant association of earlier intervention with the success of IPUK therapy was noted. Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK. Minocycline pleurodesis was subsequently performed for the 29 IPUK responders. Eighteen patients were followed up until death, with a median survival of 6.5 months. The other remained alive at the time of analysis with a median follow-up of 5 months. Two patients had an immediate failure of pleurodesis at 1 month. Three relapses occurred at 3, 4, and 7 months from pleurodesis, respectively. Twenty-three patients (79.3%) had lifelong pleural symphysis, including 21 having loculated MPEs and two having trapped lungs, respectively. Compared with the historical control group, the IPUK study group had significantly greater improvement on chest radiography and a shorter duration of pleural drainage.
These results suggest that IPUK is a safe and useful nonsurgical adjunct therapy for loculated MPEs or trapped lungs in medically inoperable cancer patients.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2006; 1(5):460-7. · 4.55 Impact Factor
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Gabriel N Hortobagyi,
Jaime de la Garza Salazar,
Kathleen Pritchard,
Dino Amadori,
Renate Haidinger,
Clifford A Hudis,
Hussein Khaled, Mei-Ching Liu,
Miguel Martin,
Moise Namer,
Joyce A O'Shaughnessy,
Zhen Zhou Shen,
Kathy S Albain
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ABSTRACT: Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.
Clinical Breast Cancer 01/2006; 6(5):391-401. · 2.38 Impact Factor
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ABSTRACT: We report the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan, defined according to the WHO classification. Data including age and gender of the patients, clinical staging and disease courses were collected for 598 cases of malignant lymphomas. The results showed that the epidemiological characteristics of malignant lymphomas in Taiwan are similar to those in other Asian countries except for a lower incidence rate of T/NK cell lymphoma.
Haematologica 01/2006; 90(12):1703-5. · 6.42 Impact Factor
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ABSTRACT: Neoadjuvant concomitant chemoradiotherapy has been used in cases of locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. Preoperative staging is essential for planning and providing optimal therapy. The purpose of this study is to determine the accuracy of staging with magnetic resonance imaging and to define any factors that interfere in interpretation of images obtained after preoperative chemoradiation therapy.
Thirty-six patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed six to eight weeks later by radical surgery. Preoperative magnetic resonance images were reinterpreted by one radiologist and the results compared with histopathologic staging.
T-level downstaging occurred in 10 of 36 patients (28 percent), and N-level downstaging occurred in 29 of 36 patients (80 percent) after completion of chemoradiation therapy. Pathologic complete remission after chemoradiotherapy occurred in five patients (12 percent). Of the 36 patients, 17 (47 percent) were overstaged and 2 (6 percent) were understaged in T-level, whereas 10 patients (28 percent) were overstaged and 3 patients (8 percent) were understaged in N-level. The accuracy of magnetic resonance imaging for determining depth of wall invasion was 47 percent, with 64 percent accuracy for nodal staging.
Magnetic resonance imaging is commonly used in staging of pelvic malignancies because of its fine resolution, but chemoradiotherapy may decrease its accuracy. Thickening of the rectal wall after radiation by marked fibrosis, and peritumoral infiltration of inflammatory cells and vascular proliferation may contribute to overestimation of stage. By contrast, pathologic residual cancer beneath normal mural structure after chemoradiation therapy may result in understaging of rectal cancer.
Diseases of the Colon & Rectum 02/2005; 48(1):23-8. · 3.13 Impact Factor
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ABSTRACT: Postgastrectomy patients undergoing chemoradiation risk chemoradiation-induced liver disease (CRILD). The objectives of this study were to investigate dosimetric implications and assess biologic susceptibility to CRILD in these patients.
Sixty-two patients with Stage IB-IV gastric/gastroesophageal adenocarcinoma without metastases underwent radical total/subtotal gastrectomy; regional lymph node dissection; and postoperative, adjuvant, concomitant chemoradiotherapy (CCRT). Among these, 8 patients developed CRILD (defined as Grade 3-4 liver toxicity), and 11 patients were chronic hepatitis B virus (HBV) carriers (HBV+). Chemotherapy consisted of 1 cycle of etoposide, leucovorin, and 5-fluorouracil (ELF); followed by 5 weekly high doses of 5-fluorouracil (2000-2600 mg/m2) and leucovorin concurrent with radiotherapy (median dose, 45 grays [Gy] to the tumor bed/regional lymphatics); followed by 3 cycles of ELF separated by a 21-day interval. Patients were followed for > or = 4 months after CCRT. Patient-related and dosimetric factors were correlated with CRILD.
HBV+ status was the only independent factor associated with CRILD. HBV+ patients had a higher CRILD incidence (6 of 11 patients vs. 2 of 51 patients; P < 0.001). HBV-negative patients with CRILD were recipients of a higher mean liver dose (MLD) (23.8 Gy vs. 15.2 Gy; P = 0.009) and a higher volume fraction of liver that received > 30 Gy (36.5% vs. 19.7%; P = 0.009) compared with noncarriers without CRILD, but no MLD difference was found between HBV+ patients with or without CRILD. Moreover, in four of six carriers with CRILD, HBV infection was reactivated during CRILD. Two of the toxicities were fatal.
HBV carriers had a higher incidence of CRILD after postgastrectomy CCRT, probably related to HBV reactivation. Dosimetric parameters modulated the risk of CRILD in noncarriers, but not in carriers. These factors deserve attention in CRILD/HBV+ patients, and the underlying pathogenesis warrants investigation.
Cancer 11/2004; 101(9):2126-33. · 4.77 Impact Factor
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M.S. Jason Chia-Hsien Cheng M.D,
Mei-Ching Liu M.D,
Stella Y. Tsai M.D,
Wei-Tse Fang M.D,
James Jer-Min Jian M.D,
Juei-Low Sung M.D,
Jason Chia‐Hsien Cheng, Mei‐Ching Liu,
Stella Y. Tsai,
Wei‐Tse Fang,
James Jer‐Min Jian,
Juei‐Low Sung
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ABSTRACT: BACKGROUND
Postgastrectomy patients undergoing chemoradiation risk chemoradiation-induced liver disease (CRILD). The objectives of this study were to investigate dosimetric implications and assess biologic susceptibility to CRILD in these patients.METHODS
Sixty-two patients with Stage IB–IV gastric/gastroesophageal adenocarcinoma without metastases underwent radical total/subtotal gastrectomy; regional lymph node dissection; and postoperative, adjuvant, concomitant chemoradiotherapy (CCRT). Among these, 8 patients developed CRILD (defined as Grade 3–4 liver toxicity), and 11 patients were chronic hepatitis B virus (HBV) carriers (HBV+). Chemotherapy consisted of 1 cycle of etoposide, leucovorin, and 5-fluorouracil (ELF); followed by 5 weekly high doses of 5-fluorouracil (2000–2600 mg/m2) and leucovorin concurrent with radiotherapy (median dose, 45 grays [Gy] to the tumor bed/regional lymphatics); followed by 3 cycles of ELF separated by a 21-day interval. Patients were followed for ≥ 4 months after CCRT. Patient-related and dosimetric factors were correlated with CRILD.RESULTSHBV+ status was the only independent factor associated with CRILD. HBV+ patients had a higher CRILD incidence (6 of 11 patients vs. 2 of 51 patients; P < 0.001). HBV-negative patients with CRILD were recipients of a higher mean liver dose (MLD) (23.8 Gy vs. 15.2 Gy; P = 0.009) and a higher volume fraction of liver that received > 30 Gy (36.5% vs. 19.7%; P = 0.009) compared with noncarriers without CRILD, but no MLD difference was found between HBV+ patients with or without CRILD. Moreover, in four of six carriers with CRILD, HBV infection was reactivated during CRILD. Two of the toxicities were fatal.CONCLUSIONSHBV carriers had a higher incidence of CRILD after postgastrectomy CCRT, probably related to HBV reactivation. Dosimetric parameters modulated the risk of CRILD in noncarriers, but not in carriers. These factors deserve attention in CRILD/HBV+ patients, and the underlying pathogenesis warrants investigation. Cancer 2004. © 2004 American Cancer Society.
Cancer 10/2004; 101(9):2126 - 2133. · 4.77 Impact Factor
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ABSTRACT: The prognosis for metastatic colorectal cancer is grave. Whether to perform surgical resection or palliative treatment remains controversial for this advanced disease. In this retrospective study, we collected data from patients with Stage IV colorectal cancer to identify prognostic factors for predicting selection criteria for surgical treatment in patients with metastatic disease.
A retrospective chart review was performed for patients treated from 1992 to 1999 from the Koo Foundation Sun Yat-Sen Cancer Center Tumor Registry. Seventy-four patients were identified as having Stage IV disease at the time of diagnosis. Data concerning the patients' demographics, laboratory results, operative procedure, mortality, morbidity, and survival were collected. Independent variables and survival time were analyzed by the independent t-test method. The difference was considered statistically significant at P < 0.05.
Overall survival time for the patients with Stage IV colorectal cancer was 16.1 months. Survival in the curative resection group was significantly longer than that in the noncurative group (31.9 vs. 12.7; P < 0.016). The operative mortality and morbidity rates were 5.6 percent (4 of 71) and 21.1 percent (15 of 71), respectively. The two most common complications were leakage at the site of anastomosis and urinary tract infection. Based on these results, we conclude that patients older than 65 years, with metastases at multiple sites, intestinal obstruction, preoperative carcinoembryonic antigen level > or =500 ng/ml, lactate dehydrogenase > or =350 units/liter, hemoglobin <10 mg/dl, or hepatic parenchymal replacement by tumor >25 percent have poor prognosis for surgical intervention.
Whether to perform primary tumor resection in patients with asymptomatic Stage IV colorectal cancer remains controversial; however, the more aggressively we perform radical resection and metastasectomy to selected patients, the more survival benefits the patients obtain.
Diseases of the Colon & Rectum 01/2004; 46(12):1646-52. · 3.13 Impact Factor
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ABSTRACT: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT).
Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months.
Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis.
LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.
International Journal of Radiation OncologyBiologyPhysics 03/2002; 52(4):980-8. · 4.11 Impact Factor
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ABSTRACT: To evaluate the efficacy of postmastectomy radiation therapy (PMRT) for prophylaxis against locoregional recurrence in high-risk breast cancer patients, and the rate of complication associated with such treatment, we retrospectively reviewed 79 breast cancers in 78 patients, who were given therapy (PMRT) between April 1990 and March 1995. Radiation doses were 46-50 Gy in 2-Gy fractions. High-risk factors included primary tumor (≥5 cm) in 19 (24.1%) patients, positive axillary lymph nodes (≥4) in 56 (70.9%) patients, positive or close (≤2 mm) surgical margins in 14 (17.7%) patients, and central or inner quadrant tumor with positive axillary nodes and lymphovascular invasion in seven (8.9%) patients. Adjuvant chemotherapy was also given to 69 of 78 (88.5%), patients and hormonal therapy to 41 of 78 (53.7%) patients. The median follow-up time was 25 months (range, 7-66 months) after mastectomy. Our study revealed that locoregional failure as the first site of failure occurred in only one of 78 (1.3%) patients. Relapse-free survival at 3 years was 67.7% [95% confidence interval (CI), 52.0-81.3], and overall survival was 76.9% (95% CI, 63.3-90.6). The incidence of radiological evidence of lung fibrosis increased significantly in patients whose internal mammary chain was included in the radiation field. The occurrence of lung fibrosis can be reduced by changing radiation treatment technique and keeping central lung distance (CLD) of tangential field to ≤2.8 cm in tangential field technique or ≤1.4 cm in tangential with a separate internal mammary field technique. We concluded that the risk of locoregional recurrence in high-risk breast cancer patients can be much reduced by PMRT. With careful selection of radiation treatment fields, radiotherapy technique, and limitation of CLD to ≤2.8 cm in tangential technique or ≤1.4 cm in separate technique, the risk of symptomatic radiation pneumonitis is minimal. PMRT should be recommended for breast cancer patients who are at high risk for locoregional recurrence.
American Journal of Clinical Oncology 01/1998; 21(1):12-17. · 2.01 Impact Factor
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ABSTRACT: Granulocytic sarcoma is an extramedullary tumor of myeloproliferative precursors and may involve multiple sites of body. The role of gallium scan in patients with granulocytic sarcoma is uncertain. This article demon-strates the findings of gallium-67 scan on a case with granulocytic sarcoma that was proved by histopatholo-gy and immunohistology. The gallium-67 scan revealed multiple focal areas with intensively abnormal uptake of gallium-67 in the ethmoid, right nasal, right maxillary, bilateral neck, bilateral chest, mediastinal, abdominal, pelvic and bilateral renal regions. The gallium-67 scan indicated the disease was widespread and suggested poor prognosis of the patient. This article delineates granulocytic sarcoma has high affinity for gallium-67 and suggests gallium-67 scan has the role for the whole body evaluation of the extension of granulocytic sarco-ma. Ann Nucl Med Sci 2001;14:125-128 Granulocytic sarcoma is an extramedullary tumor of myeloid precursors [1]. Because the cut surface of the tumor is greenish, granulocytic sarcoma is also called chloroma [1]. The histopathology of granulocytic sarcoma is variable and may include blastic, immature or differentiated cells depend-ing on the level of myeloid maturation [1,2]. Granulocytic sarcoma is a widespread disease and may involve orbit, nasal sinus, paranasal sinus, facial bones, lymph nodes, breast, skin, central nervous system, respiratory, gastrointestinal or genitourinary tracts [1-4]. Gallium-67 scan has been widely used to evaluate malignant tumors, including malignant lymphoma, melanoma, lung malignancy and soft tissue sarcoma [5-10]. However, there were only few case reports of using gallium-67 scan to evaluate patients with granulocytic sarcoma in the literature [11-13]. The role of gallium scan in patients with granulocytic sarcoma is uncertain. We describe intense galli-um-67 uptake at multiple regions in a case with granulocytic sarcoma. Case Report A 31-year-old male patient was a case of acute myeloid leukemia (AML) which was diagnosed at age of 18. This patient had received chemotherapy and radiotherapy for the treatment of AML, and the disease was complete remission after treatment. The patient, however, followed up irregularly at our clinic after the complete remission of the disease. Because of eye pain and neck masses, this patient admitted to our hospital again for further management. During this admission, physical examination revealed multiple masses in bilateral upper and lower neck regions. Magnetic resonance imaging (MRI) of head and neck revealed multiple tumors involved right ethmoid, left and right maxillary sinuses and also revealed multiple enlarged lymph nodes in the bilateral upper and lower neck regions (Figure 1).
