Stage IIB Disease Research Articles

Acinar Cell Carcinoma of the Pancreas: An Institutional Series of Resected Patients and Review of the Current Literature

IntroductionAcinar cell carcinoma (ACC) is a rare, malignant neoplasm with a generally poor prognosis. We report our institutional series of 14 patients with ACC to determine current guidelines for their evaluation and treatment. Materials and MethodsThe Johns Hopkins pathology prospective database was reviewed from 1988 to 2006 to identify patients with pancreatic neoplasms possessing features of acinar cell differentiation. Retrospective review and follow-up was performed for each patient. ResultsFourteen patients with ACC were identified with a median age of 57 years. All patients presented with abdominal pain or discomfort with none showing evidence of lipase hypersecretion syndrome. Each patient underwent surgical resection, including nine pancreaticoduodenectomies and five distal pancreatectomies. Median tumor size was 3.9 cm with 12 patients found to have stage IIB disease or worse. Four patients underwent neoadjuvant chemoradiation. Eight of the fourteen patients developed recurrent disease. Overall median survival and disease-free survival were 33 and 25 months, respectively, as compared to a median survival of 18 months for pancreatic adenocarcinoma. ConclusionAcinar cell carcinomas are rare, aggressive neoplasms that are difficult to diagnose and treat. Operative resection represents the best first-line treatment. These lesions have a better prognosis than the more common pancreatic adenocarcinomas.

Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non–Small-Cell Lung Cancer Guideline

To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC). The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.

R0 resection for ductal pancreatic cancer—Japanese experience

Since 1981, the Japan Pancreas Society (JPS) and National Cancer Center have jointly maintained the nationwide pancreatic cancer registry. Currently, there are 28,655 cases registered, with 12,608 cases of histologically confirmed invasive pancreatic cancer. Since the last revision of the International Union Against Cancer (UICC) classification in 2002, the survival analysis of the patients registered from 2001 to 2004 became possible for the first time. Using this detailed database, the rational of R0 resection was investigated. From 2001 to 2004, 2617 cases of histologically confirmed invasive ductal carcinoma of the pancreas were registered. According to the UICC classification, R0 resection becomes problematic mostly in UICC stage IIa and IIb. Of 1039 patients who underwent pancreatectomy for the tumor in the head of the pancreas, 160 had UICC stage IIa disease, and 468 had UICC stage IIb disease. The relationship between the survival and the extent of disease, together with portal vein (PV) resection, plexus (PL) resection, were analyzed. PV, retroperitoneal, and PL infiltration had a significant impact on the accomplishment of R0 resection in univariate and multivariate analyses. There was no advantage of PV resection for both PV (−) and PV (+) disease among UICC stage IIa or IIb patients, suggesting no benefit of prophylactic PV resection. Similarly, survival depends on PL invasion but not on combined resection of PL. There was no survival benefit associated with the extent of lymph node dissection. Survival among patients treated in the 2000s, after the introduction of gemcitabine in Japan, is significantly better than that of patients treated in the 1980s and 1990s. Although survival after pancreatectomy depends on the extent of disease rather than the surgical procedures, the chronologic improvement in survival indicates that chemotherapy had a significant impact on survival; development of new treatment modalities is awaited.

Factors Associated with Advanced Disease Stage at Diagnosis in a Population-based Study of Patients with Newly Diagnosed Breast Cancer

Breast cancer is diagnosed at a younger age and a more advanced stage in African-American women than in White women. The authors investigated the effects of several factors, including race, on stage of breast cancer in women aged 20-54 years living in Atlanta, Georgia, and diagnosed between 1990 and 1992. A total of 251 African-American and 580 White women were interviewed and their medical records reviewed. By use of polytomous logistic regression, factors possibly influencing stage and racial differences in stage were studied. In African-American women, the odds of stage III/IV breast cancer at diagnosis were almost four times the odds in White women (odds ratio = 3.79, 95% confidence interval: 2.45, 5.89) and approximately two and one-half times for stage IIA or stage IIB disease (odds ratio = 2.57, 95% confidence interval: 1.66, 3.99; odds ratio = 1.94, 95% confidence interval: 1.31, 2.86, respectively). These racial differences appeared to be largely explained by insurance status, poverty, history of mammography, method of tumor detection, and obesity. Interventions targeting these factors could potentially lower the stage at diagnosis for African-American breast cancer patients and, in doing so, improve their survival and other outcomes.

Up-to-date management of lymph node metastasis and the role of tailored lymphadenectomy in cervical cancer

Lymph node metastasis (LNM), together with parametrial infiltration and positive surgical margins, is an important prognostic factor in cervical cancer. The incidence of LNM increases with International Federation of Gynecology and Obstetrics (FIGO) stage, with rates being 12%-22% in stage Ib, 10%-27% in stage IIa, and 34%-43% in stage IIb. Radical hysterectomy and pelvic lymphadenectomy are widely used treatments for early-stage (Ib to IIa) cervical cancer, as well as for stage IIb disease, in some European and Asian countries. In several types of cancer, the therapeutic significance of systematic lymphadenectomy has been demonstrated by recent reports showing that a larger number of lymph nodes removed relates to better survival. In cervical cancer, a significant relationship between the number of lymph nodes removed and disease-free survival has been reported in node-positive patients. Preoperative evaluation of nodal status with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging techniques is not sensitive enough to replace the histological examination of dissected nodes. The sentinel node procedure may be an alternative to systematic lymphadenectomy to reduce treatment-related morbidity, but more work on this is needed. Although the presence of LNM does not change FIGO staging, it will modulate postoperative therapy. Progression-free and overall survivals were significantly improved by the addition of chemotherapy to adjuvant radiotherapy after radical hysterectomy and lymphadenectomy. Adjuvant chemotherapy combined solely with radical hysterectomy and systematic lymphadenectomy may also provide a survival benefit. In conclusion, efforts to establish more tailored surgical strategies, by introducing advanced imaging technologies and molecular diagnostic procedures, are needed for cervical cancer.

Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma

To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes. Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated. Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE. Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities

Traditionally, surgery is considered the best treatment for oesophageal cancer in terms of locoregional control and long-term survival. However, survival 5 years after surgery alone is about 25%, and, therefore, a multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, could prove necessary. The role of each of these treatments in the management of oesophageal cancer is under intensive research to define optimum therapeutic strategies. In this report we provide an update on treatment strategies for resectable oesophageal cancers on the basis of recent published work. Results of the latest randomised trials allow us to propose the following guidelines: surgery is the standard treatment, to be used alone for stages I and IIa, or possibly with neoadjuvant chemotherapy or chemoradiotherapy for stage IIb disease. For locally advanced cancers (stage III), neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is appropriate for adenocarcinomas. Chemoradiotherapy alone should only be considered in patients with squamous-cell carcinomas who show a morphological response to chemoradiotherapy, and produces a similar overall survival to chemoradiotherapy followed by surgery, but with less post-treatment morbidity. Although the addition of surgery to chemotherapy or chemoradiotherapy could result in improved local control and survival, surgery should be done in experienced hospitals where operative mortality and morbidity are low. Moreover, surgery should be kept in mind as salvage treatment in patients with no morphological response or persistent tumour after definitive chemoradiotherapy.

Vorinostat for Treatment of Cutaneous Manifestations of Advanced Primary Cutaneous T-Cell Lymphoma

To discuss vorinostat approval for treatment of cutaneous manifestations of advanced cutaneous T-cell lymphoma (CTCL). Data from 1 single-arm, open-label, multicenter pivotal trial and 11 other trials submitted to support the new drug application for vorinostat in the treatment of advanced primary CTCL were reviewed. The pivotal trial assessed responses by changes in overall skin disease score using a severity-weighted assessment tool (SWAT). Vorinostat could be considered active in CTCL if observed response rate was at least 20% and the lower bound of the corresponding 95% confidence interval (95% CI) excluded 5%. Patients reported pruritus relief using a questionnaire and a visual analogue scale. The pivotal trial enrolled 74 patients with stage IB or higher CTCL. Median number of prior treatments was 3, and 61 patients (82%) had stage IIB or higher disease. The objective response rate in the skin disease assessed by change in the overall SWAT score from the baseline was 30% (95% CI, 18.5 to 42.6) in patients with stage IIB or higher disease. Median response duration (end of response defined by 50% increase in SWAT score from the nadir) was 168 days. Median time to tumor progression was 148 days for overall population and 169 days for patients with stage IIB or higher disease. Assessment of pruritus relief was considered unreliable. Vorinostat showed activity in CTCL, and skin responses were a clinical benefit. Vorinostat was approved for treatment of cutaneous manifestations of CTCL. A nonblinded, single-arm trial did not allow a reliable assessment of pruritus relief.

Merkel cell carcinoma of the head and neck: Is adjuvant radiotherapy necessary?

Controversy exists regarding the optimal management of patients with Merkel cell carcinoma. The primary aim of this study was to determine whether combined treatment with surgery and radiotherapy improves outcome in a multi-institutional cohort of patients with Merkel cell carcinoma of the head and neck. The secondary aims were to determine by stage, which patients derive benefit from combined therapy and to identify predictors for survival on multivariable analysis. A retrospective analysis of 110 patients with Merkel cell carcinoma of the head and neck was performed. Data were collected from 3 tertiary care institutions (Westmead Hospital, Sydney, Australia; Princess Margaret Hospital, Toronto, Canada; Royal Prince Alfred Hospital, Sydney). There were 78 males and 32 females, median age was 70 years, and mean follow-up of survivors was 2.3 years. Sixty-six patients underwent combined treatment, and 44 patients had either surgery or radiotherapy alone. Analysis by stage was performed using 2 staging systems. Local and regional control at 5 years was 84% and 69%, respectively. Combined treatment improved both local (p = .009) and regional control (p = .006). Overall and disease-specific survival at 5 years was 49% and 62%, respectively. Combined treatment was associated with significantly better disease-free survival on univariable analysis (p = .013) When analyzed by stage, patients with stage IIb (primary >1 cm, node negative) disease who underwent combined treatment had improved disease-free (p = .005) and disease-specific survival (p = .035). Predictors of survival on multivariable analysis were age >70 years (HR 6.19, p < .001), primary tumor size >1 cm (HR 7.55, p < .001), number of nodal metastases divided into none, <or= 2 and >2 (HR 3.71 per stratum, p < .001). When analyzed with age and disease stage, treatment modality trended toward significance as a predictor of disease-specific (p = .081) and overall survival (p = .076). Disease stage was the most powerful independent predictor on Cox regression (HR 5.43 per stratum, p < .001). Merkel cell carcinoma is an aggressive cutaneous malignancy. Age and disease stage are the most important predictors of survival. Combined surgery and radiotherapy improves both locoregional control and disease-free survival. Patients with stage II disease appear to derive the greatest benefit from adjuvant radiotherapy, including improved disease specific survival.

Hand-Assisted Laparoscopic Retroperitoneal Lymph Node Dissection for Nonseminomatous Testicular Cancer

We describe our initial experience with hand-assisted laparoscopic retroperitoneal lymph node dissection for nonseminomatous testicular cancer. Between April 2002 and December 2004, 10 patients with testicular tumor were operated on, 6 on the right side and 4 on the left side. Eight patients were in clinical stage I, one patient was in clinical stage IIA, and one patient was in clinical stage IIB disease. Depending on the tumor site, a 6-7 cm mid-lower or -upper laparotomy was done, the HandPort (Smith and Nephew, Andover, MA) was placed in the abdominal wall, and the left hand of the surgeon was inserted into the abdomen. Four laparoscopic ports were also inserted. The ascending or descending colon was mobilized completely. The retroperitoneal lymph nodes were dissected and removed according to the modification of Weissbach and colleagues. The average operative time was 258 min (range, 150-432 min). One patient required re-operation because of postoperative bleeding. The average postoperative hospital stay was 3.5 (range, 3-10) days. Patients with stage IIA or IIB disease on histopathology received 2-3 courses of combined chemotherapy. Antegrade ejaculation was preserved in all patients. During follow-up that ranged from 9 to 36 months, there was no local recurrence or distant metastasis. Hand assistance makes the laparoscopic operation simpler, faster, and safer. A 6-7 cm muscle-splitting incision should be advantageous for patients compared to the xyphopubic laparotomy of the open procedure. To our knowledge this is the first report on hand-assisted laparoscopic retroperitoneal lymph node dissection.

Brain metastasis from cervical carcinoma

The aim of this study was to describe the features of patients with brain metastasis from cervical cancer. Twelve patients with brain metastasis from cervical cancer were identified. Information regarding symptoms, treatment, and survival was analyzed. The incidence of brain metastasis in our population was 0.77%. Median patient age at initial diagnosis of cervical cancer was 43.5 years (range 29-57 years) compared with 44.5 years (range 31-58 years) at identification of brain metastasis. Six patients had FIGO stage IB disease; three had stage IIB disease; and one each had stage IIIA, IIIB, and IVB disease. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 17.5 months (range 1.1-96.1 months). All but one patient presented with neurologic symptoms. Eight patients received whole-brain irradiation and steroids, three received steroids alone, and one underwent surgery, followed by irradiation. All the patients who received whole-brain irradiation experienced improvement in their symptoms. Median survival from diagnosis of brain metastasis to death was 2.3 months (range 0.3-7.9 months). Five patients who received chemotherapy after brain irradiation had a median survival of 4.4 months compared to 0.9 months for those who received no additional treatment after brain irradiation (P= .016). Most patients with brain metastasis from cervical cancer presented with neurologic sequelae. Brain irradiation improved these symptoms. Survival after diagnosis of brain metastasis was poor; however, patients who received chemotherapy after brain irradiation appeared to have improved survival.

Chemoradiation therapy in pregnant patients treated for advanced-stage cervical carcinoma during the first trimester of pregnancy: report of two cases

Two patients treated using chemoradiation therapy (CRT) (with fetus in utero) for advanced-stage squamous cell cervical carcinoma diagnosed during the first trimester of pregnancy are reported. One patient with a stage IVA disease diagnosed at 12 weeks of gestation was treated by exclusive CRT with the fetus in utero. She recurred 20 months after the end of the treatment. The second patient had a stage IIB disease diagnosed at 12 weeks of gestation and was treated by CRT with the fetus in utero followed by completion surgery (radical hysterectomy and para-aortic lymphadenectomy) due to the presence of a suspicious residual disease. No residual disease was observed during the histologic analysis of hysterectomy and nodes specimens. This patient is alive and free of disease 24 months after surgery. Our observations could suggest that CRT in pregnant patients with fetus in utero is feasible without major short-term toxicity. Such management could be proposed in patients with a bulky cervical cancer diagnosed during the first trimester of the pregnancy. Management of the uterine evacuation depends on the local tumor spread.

Recurrence Pattern and Proposed Surveillance Protocol Following Post-Chemotherapy Retroperitoneal Lymph Node Dissection

We evaluated the recurrence pattern in patients with nonseminomatous germ cell tumors treated with post-chemotherapy retroperitoneal lymph node dissection and determined the optimal surveillance strategy in these patients. Between 1980 and 2003, 236 patients with clinical stage IIA-III nonseminomatous germ cell tumors underwent post-chemotherapy retroperitoneal lymph node dissection. Patients with increased preoperative tumor markers (alpha-fetoprotein greater than 15 ng/ml and/or beta-human chorionic gonadotropin greater than 2.2 U/ml) were excluded from study resulting in 198 patients for analysis. We retrospectively reviewed medical records for pertinent clinical and treatment related outcomes. In our patient population recurrence developed in 45 (23%) patients and 22 (11%) died of disease at a median followup of 41 months (range 6 to 250) after retroperitoneal lymph node dissection. The clinical stage of testis cancer was IIA in 17, IIB in 49, IIC in 83 and III in 49 patients. Of the 45 patients with postoperative recurrence, 16 had concomitant multiple sites of recurrence with a total of 64 sites reported. Of the cases of recurrence 21 (46.7%) were in those of clinical stage III, 18 (40%) stage IIC and 6 (11.8%) stage IIB disease. The most frequent site of recurrence was the chest (32, 49%), followed by the abdomen (14, 22%), supraclavicular lymph nodes (8, 13%), brain (5, 8%) and other sites (5, 8%). Based on the recurrence pattern we propose stage specific surveillance guidelines for the followup of patients after post-chemotherapy retroperitoneal lymph node dissection. These guidelines help identify patients at high risk for disease progression and, thus, requiring more stringent postoperative followup.

Initial Treatment of CD20+ Lymphocyte Predominant Hodgkin Lymphoma with Chemotherapy and the Monoclonal Antibody Rituximab-Mabthera Is Effective and Well Tolerated - Case Report.

Patients with lymphocyte-predominant Hodgkin disease (LPHD) often present at an early stage with slow disease progression. Although 96% of LPHD patients experience a complete remission (CR) upon first line treatment, many relapses occur. CD20+ is strongly expressed by malignant cells in LPHD, but so far there is limited information regarding the efficacy of rituximab in this patient population. We report 46-year-old woman who presented in 2004 with left cervical lymphadenopathy and weight loss.Case report: Biopsy confirmed a diagnosis of LPHD(stage IIB disease), immunohistochemistry revealed that >30% of malignant cells were CD20+, and a bulky mediastinal mass was observed by computer tomography (CT). Blood counts, erythrocyte sedimentation rate, albumin and lactate dehydrogenate were normal. The patient was treated with rituximab and ABVD (doxorubicin 25mg/m2, bleomycin 10mg/m2, vinbalstine 6mg/m2, dacarbazine 375mg/m2, six cycles). Rituximab was administered (375mg/m2) one day before chemotherapy (50mg/h for one hour and gradually escalated to a maximum of 400mg/h). Treatment was well tolerated and there were no complications. The patient was assessed immediately following treatment and every three months for the following year, by physical examination, CT, bone marrow biopsy and routine analyses. A detectable tumor mass was no observed by CT for the follow up of 2 years, the patient remains in complete remission.Conclusion: Our case report suggests that Rituximab is both safe and effective in patients with CD20+ LPHD. Further studies with Rituximab are warranted in this patient population.

Oral Forodesine (Bcx-1777) Is Clinically Active in Refractory Cutaneous T-Cell Lymphoma: Results of a Phase I/II Study.

Background: Forodesine is a potent, rationally designed purine nucleoside phosphorylase (PNP) inhibitor that is orally bioavailable. IV forodesine has shown clinical activity in patients with cutaneous T-cell lymphoma (CTCL). The objective of this phase I/II study was to evaluate the safety, PK profile, and efficacy of oral forodesine in patients with refractory CTCL.Methods: An open-label dose-escalation study of fordesine, 40 to 320 mg/m2 qd for 4 weeks, was undertaken to evaluate the safety and PK profile of oral forodesine, followed by an investigation of the expansion of the optimal biologic dose (dose with maximum PNP inhibition and elevation of plasma deoxyguanosine levels) to assess efficacy. Previously treated, refractory CTCL patients with stage IB or greater disease were eligible for participation. The primary end point was objective response (OR) = complete response [CR] plus partial response [PR], as measured by the severity-weighted assessment tool (SWAT; see Figure) and physicians' global assessment (PGA)Results: Overall, 37 patients were treated, including 14 patients in the dose-escalation portion of the study. No dose-limiting toxicities were observed with target doses of ≤320 mg/m2; thus, a maximum tolerated dose was never defined. Based on PK/PD results, an 80 mg/m2 qd dose was identified as the optimal biologic dose, and this ongoing study was expanded to enroll a total of 28 patients (median age, 64 yr; range, 28–81 yr). The OR rate was 53.6% (15/28 patients; 2 [7.1%] with a CR and 13 [46.4%] with a PR). The proportion of patients with stage IIB or greater disease was 19/28 (67.9%). Response in this population was seen in 10 (52.6%) of the 19 patients (1 [5.3%] with a CR and 9 [47.4%] with a PR). The percent change in SWAT score from baseline as a function of time demonstrated a progressive decrease over a 24-week period. To-date, 12 (42.9%) of 28 patients have completed ≥4 months of treatment. Safety data were recorded for all 37 patients treated with forodesine. The most common adverse events classified as grade 2 or less, without regard to causality, were nausea (30%), dizziness (22%), pruritus (22%), fatigue (19%), headache (19%), peripheral edema (19%), and pyrexia (16%). The only adverse event classified as grade 3 or greater, without regard to causality, and occurring in at least two patients, was lymphopenia, which was observed in two patients (5%).Conclusions: Oral forodesine is effective in the treatment of refractory CTCL patients and has an encouraging safety profile. [Display omitted]

Operative Indications for Lung Cancer with Satellite Lesions

In deciding the surgical treatment for lung cancer, it is important to differentiate between a small satellite lesion that is probably benign, a pulmonary metastatic lesion, or a double cancer. The operative indications for lung cancer with small satellite lesions detected on preoperative helical computed tomography were retrospectively examined. We collected 43 small nodules < or = 1 cm in diameter from 32 patients. A definitive diagnosis was made by follow-up computed tomography in 3 of 19 ipsilateral lesions and in 9 of 24 contralateral lesions. The final diagnosis of the satellite lesions was malignant in 13 and benign in 30. The 13 malignant lesions consisted of 2 pulmonary metastases and 11 double cancers. Two patients with stage IIb and IIIb disease on clinical staging of the main tumor had pulmonary metastases. Patients with clinical stage I disease had a higher probability that the small lesions were benign or double cancers than those with advanced disease beyond clinical stage I.

Laparoscopically assisted radical vaginal hysterectomy (Coelio-Schauta): a comparison with open Wertheim/Meigs hysterectomy

The objective of this study was to compare the safety, efficacy, and short-term benefits of the Coelio-Schauta procedure with open Wertheim/Meigs radical abdominal hysterectomy. We retrospectively analyzed records of our first 35 consecutive patients undergoing laparoscopically assisted radical vaginal hysterectomy (LARVH) for early cervical cancer and 32 consecutive patients of open radical hysterectomy (ORH) performed between 1999 and 2005 in our institution. We analyzed patient age, bodyweight, previous abdominal surgery, operating time, blood loss, perioperative complications, postoperative bladder dysfunction, other postoperative complications, and histologic type. The FIGO stage, excision margins, node count and node status, follow-up, and recurrence rates were also taken into account. We excluded stage IA and stage II disease patients to reduce the impact of tumor size on the outcome of the surgery. This left 27 patients with stage IIB disease who had LARVH and 28 patients with stage IB disease who had ORH. These patients formed the study group. The cohorts were similar in age, bodyweight, previous abdominal surgery, histologic subtype, FIGO stage, resection margins, node count and node status, length of follow-up, and recurrence. There were statistically significant differences between LARVH and ORH for duration of surgery (mean 160 vs 132 min), intraoperative blood loss (479 vs 715 mL), hospital stay (mean 5 vs 9.3 days), postoperative complications (6 vs 20 patients), and duration of bladder catheterization (mean 4.4 vs 8.8 days). Four LARVH patients and no ORH patients had urinary tract injury that was repaired. None had long-term sequelae. Our data confirm that LARVH is a suitable alternative to ORH hysterectomy for small-volume stage IB1 cervical cancer with similar clinical efficacy and a superior postoperative recovery and postoperative morbidity profile. Urinary tract trauma is a clear risk in the early stages of the learning curve.

Evaluation of comparative survival based on the AJCC 5th and 6th editions for breast cancer staging: 25 year experience in two southwest Washington state community cancer programs

6118 Background: The revised American Joint Committee on Cancer (AJCC) sixth edition (6th ed.) cancer staging system increased stratification within breast cancer (BC) stages II and III defined by the AJCC 5th ed. system. The specific aim of this study was to determine and compare disease-free survival (DFS) for stage 0-III breast carcinoma between the 5th and 6th editions using retrospective data gathered from 1980–2004 in southwest Washington state (WA). Methods: 4,810 patients (pts) were identified using cancer registries at Saint John Medical Center in Longview, WA and Southwest Washington Medical Center in Vancouver, WA. Patients were restaged retrospectively using the 5th and 6th ed. systems. DFS was determined using the Kaplan-Meier method and compared using the log-rank test. Results: The age at diagnosis ranged 20–99 yrs, with a mean age = 60. The mean length for disease-free follow-up was 224 mos. Stage 0 and stage 1 criteria were unchanged between editions, and 10-yr DFS was 94% and 87% for stage 0 and stage 1, respectively. In stage II pts, 13% (199/1,519) were upstaged to stage III by the 6th ed. criteria, significantly improving the 10-yr DFS for stage II from 66% (5th ed.) to 72% (6th ed; p = 0.003). The majority, 85% (167/199), of pts upstaged were from the 539 classified as stage IIb disease by the 5th ed. This accompanied an increase in the 10-year DFS for stage IIb from 54% (fifth) to 62% (sixth; p = 0.046). The number of pts with stage III disease increased from 313 to 588 in the 6th ed. 10-year DFS increased from 30% to 36% (p = 0.025), respectively. Most of this increase resulted from changes within stage IIIa, as DFS increased from 32% to 41% (p = 0.046). When compared, DFS outcomes between stage IIIb and IIIc were not found to be statistically significant (p = 0.501). Conclusions: The AJCC 6th ed. system for BC provides greater distinctions between stages compared to the 5th ed., and reclassification results in significant changes in projected outcomes. However, the addition of the IIIc substage does not seem to show the same significant distinction when compared to the existing stage IIIb substage in outcomes. No significant financial relationships to disclose.

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.

Polymorphism in Cytokine Genes as Prognostic Marker in Hodgkin's Lymphoma.

It is thought that the production of a variety of cytokines by the malignant Reed-Sternberg cells and the surrounding tissue contributes to the abnormal immune response which is a clinical and pathological feature in Hodgkin's lymphoma. Single nucleotide polymorphism in the 5′-promoter region of cytokine genes are key factors for cytokine production and may modify the biology of the disease. Recently, differences in the prognosis according to the Interleukin-10 (IL-10) genotype have been shown in patients with diffuse large B cell lymphomas (Lech-Maranda et al, Blood 2004; 103:3529). We assessed the distribution of frequencies of polymorphic allele variants in the genes of IL-10 (A-1082G and C-592A), TNF-alpha (C-863A and G-308A) and IL-6 (G-174C) in 218 patients with Hodgkin's lymphoma and analysed for associations with patient charcteristics and prognosis. The polymorphism were analyzed using a multiplex amplification and mismatched polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique as described by Tseng et al (Tissue Antigens 2002; 59:280). DNA was extracted either from peripheral blood or paraffin-embedded lymph node biopsies from 218 patients with Hodgkin's lymphoma (median age 32 years, range 13–71 years; 104 females and 114 males). 206 patients were treated with standard chemotherapy regimens: 123 patients received ABVD, 33 pts a modified Stanford V regimen (substituting 6 mg/m2 metchloramine with 650 mg/m2 cyclophosphamide), 29 pts MOPP (±ABVD), 21 pts BEACOPP.The distribution of allele frequencies in Hodgkin's lymphoma at position -592 of the IL-10 gene was as follows: 43 % were homozygous for the CC genotype, 41 % were heterozygous and 16 % were homozygous for the AA genotype. The IL10 -592AA genotype was associated with a decreased progression-free survival (p=0.0057). The probability of progression-free survival at median time of observation of 4 years for patients homozygous for the IL-10 -592 AA genotype was 33 % (95 % C.I, 14–54 %), while for heterozygous patients and for patients homozygous for the −592 C allele it was 74% (95% C.I., 61–83). When the analysis was restricted to 123 patients treated with ABVD chemotherapy, essentially the same differences in progression-free survival were observed. No associations between genotype distributions of TNF alpha at position −308 and −863, IL-6 at position −174, and IL-10 at position −1082 and clinical variables and prognosis were found. In univariate analysis of established prognostic factors, stage proved to be of prognostic value in our patient group (limited disease in stage I–IIA vs advanced disease in stage IIB–IV, p=0.012) The Cox multivariate analysis showed that IL-10 -592AA genotype and stage were independent prognostic factors (p=0.01 and 0.018, respectively). Our study indicates that the cytokine genotype can predict clinical outcome in patients with Hodgkin's lymphoma and points to the importance of the genetic background of the host.