Positive Regional Nodes Research Articles

Role of Androgen Deprivation Therapy for Node-Positive Prostate Cancer

To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era. We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT. A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition. Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.

Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival

Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the association of functional polymorphisms in the VEGF gene with colorectal cancer development, prognosis, and survival. Three hundred twelve consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and five VEGF (-2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. VEGF -2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T genotype and allele frequencies were similar among patients and controls. There was a trend showing carriers of the -2578A and +936T alleles more frequent among patients with CRC, but these differences did not reach statistical significance. Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. However, the -2578AA, -634CC, and +936TT genotypes found to be related with a significantly lower overall survival in our study. In conclusion, VEGF gene polymorphisms were found to be an independent prognostic marker for Greek CRC patients.

20 PHOTODYNAMIC THERAPY IN MULTIMODALITY TREATMENT OF LOCALLY ADVANCED AND RECURRENT ORAL CANCER

Background: Long-term results of radiotherapy alone or in combined treatment with patients with locally advanced oral cancer are not very impressive with 5 year overall survival not higher than 56%. Photodynamic (PDT) therapy possesses its own anti-tumor activity and may sensitize to radioand chemotherapy. Purpose: To evaluate the potential significance of PDT in multimodality treatment of oral cancer. Materials and Methods: 35 patients (26 78 y.o.) with primary T2 4N0 1M0 and recurrent squamous cell oral cancer (tongue, superior/inferior lip, mouth basis) with contradictions to traditional radioor combined treatment were included in the current study. Photosensitizers “FOSCAN”, “FOTOLON”, “RADOCHLORIN” were used by intravenous injections, then patients were treated by light (semiconductor laser, wavelength 652 667 nm, output power 1W, light doses 50 300 J/cm2) in 3 96 h after injection. Adjuvant RT on neck lymph nodes begun on 10 14 days after PDT, in 3Gy/fraction 5 times a week, TD 30 36Gy (TDeq 40 44Gy) in N0 and 45 48Gy (TD eq 56 60Gy) in N1 patients. In 15 patients (42.9%) with primary tumour volume >3 cm3 or positive regional lymph nodes platinum-based neoadjuvant chemotherapy was used, with PDT after adequate tumour regression (tumour volume 0.5 2.5 cm3) or brachytherapy (60Co LDR, 192Ir HDR) in patients with larger tumours. Results: Objective response 30 patients (85.7%): complete response was achieved in 23 patients (65.7%), partial in 7 (20%). In 24 months period objective response was 26 patients (74.3%) patients, including cancer of lip 100%, tongue 70%, mouth basis 66%. No severe complications were recorder. Treatment had good cosmetic effect and high functional rehabilitation. Conclusion: PDT as a step of multimodality program expands the possibilities for radical treatment and improves long-term results in patients with oral cancer.

Clear cell carcinoma, not otherwise specified, of salivary glands: a clinicopathologic study of 4 cases and review of the literature

Clear cell carcinoma, not otherwise specified (CCC-NOS), is a recently described rare malignant salivary neoplasm. We report the clinicopathologic and immunohistochemical features of 4 cases. The results were then analyzed collectively with the approximate 60 cases of CCC-NOS reported in the English-language literature to define the characteristics of this unusual neoplasm. Combining our cases with those in the literature, a total of 66 cases, confirms that CCC-NOS is a low-grade malignant neoplasm with distinctive clinical and pathologic features. It arises primarily in the minor salivary glands (91% of cases), particularly in the palate or base of tongue, and usually occurs in patients >30 years of age (mean 54.2 years) with a female-to-male ratio of 1.4:1; 12.3% of patients experience local recurrences, 19.3% develop positive regional lymph nodes, 8.8% have distant metastases, and 3.5% die of the disease. Immunohistochemical study focusing on tumor differentiation was performed for our cases, and the findings support the concept that CCC-NOS is of ductal epithelial origin without myoepithelial cell participation.

Adjuvant radiotherapy for cutaneous melanoma

The purpose of the current study was to discuss the efficacy of adjuvant radiotherapy (RT) in the treatment of melanoma by reviewing the pertinent literature. The risk of locoregional recurrence after surgery alone for locally advanced melanoma is relatively high. The likelihood of a positive sentinel lymph node biopsy (SLNB) exceeds 20% for melanomas>2 mm thick and approximately>or=20% of those patients with positive SLNB will be found to have residual positive lymph nodes on completion lymph node dissection. Patients with positive regional lymph nodes have an approximately>or=20% risk of regional recurrence after surgery alone, particularly if multiple lymph nodes are involved and/or extracapsular extension is present. Postoperative adjuvant RT results in locoregional control rates of 85% to 90% or higher in high-risk patients with a modest risk of complications. The impact of adjuvant RT on survival is likely minimal.

Poorly Differentiated Colorectal Carcinoma With Invasion Restricted to Lamina Propria (Intramucosal Carcinoma): A Follow-up Study of 15 Cases

Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and therefore have no potential for metastases and local intervention (usually polypectomy) should be adequate treatment. For this reason, they are classified as "Tis" in the TNM system. It is believed that carcinomas invading the submucosa with unfavorable histology (tumors at/near the margin, and/or vascular invasion, and/or poor differentiation) require additional intervention after polypectomy, whereas those with favorable histology can be safely treated endoscopically. However, there are few data on poorly differentiated (PD) carcinomas showing invasion confined to the LP. Polypectomy is theoretically curative but in practice this has not been well demonstrated. Thus, the clinicopathologic features of 15 cases of PD CRCs with invasion limited to the LP on initial biopsies were studied to determine the best course of management for this rare subset of carcinomas. A computer search and histologic review of cases seen at Johns Hopkins Hospital was performed. Fifteen cases of PD CRC with invasion limited to the LP were identified. The clinicopathologic features of these tumors were reviewed. All 15 cases showed PD IMC with single cells infiltrating only the LP. Patients were 38 to 79 years (median, 62) of age with a male predominance (M:F=4:1). Three cases had signet ring cell differentiation, 1 had focal small cell features, and another had focal squamous differentiation. Fourteen of the cases were associated with background adenomas or adenomalike lesions including: 7 involving tubulovillous or villous adenomas, 6 involving tubular adenomas, 1 involving dysplasia associated with chronic inflammatory bowel disease. Nine of the lesions had surrounding high-grade dysplasia. One case showed no background dysplasia or adenoma. One patient was lost to follow-up and the remaining 14 were followed for 1 to 96 months (mean, 21.3 mo; median, 13 mo). Seven patients had no residual disease on follow-up colonoscopy, and no resection was performed. The remaining 7 patients were treated with partial colectomy (6) or low anterior resection (1), and of these, 5 had no infiltrating carcinoma and negative lymph nodes. One patient had a separate large colorectal (T3) carcinoma with 8/10 positive regional lymph nodes; the IMC seen on biopsy was presumably a metastasis as it was unassociated with an in situ component. Finally, the resected rectum from which an IMC had been previously detected had no residual invasive carcinoma, but the anal skin was involved by Paget disease. Thus, of the 15 cases of PD CRCs limited to the LP, 1 was a metastasis from a separate CRC and another had associated Paget disease of the anal skin. As such, even in the setting of PD carcinomas, no metastatic disease was seen arising from any of the cases that were confirmed as early primary lesions. These preliminary findings suggest that patients with isolated intramucosal PD CRCs may be managed endoscopically.

Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk

Tumor growth requires the formation of new blood vessels, a phenomenon known as angiogenesis. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). Several common polymorphisms in the VEGF-gene have been associated with different VEGF expression, production and plasma levels according to allele status, and influence the risk of developing different types of cancer. Therefore, these variants might be risk factors for colorectal cancer (CRC). In the present case-control study, VEGF genotypes of the +936 C>T, -2578 C>A and -634 G>C polymorphisms were determined in 427 patients with histologically verified CRC and 427 age and sex-matched healthy control subjects. Genotypes were analyzed by a fluorogenic exonuclease assay (TaqMan). P-value for age at diagnosis was analyzed by student's t test, P-values for tumor characteristics were determined by Pearson's Chi-square test. Threshold for significance was P<0.05. At the time of diagnoses, patients were between 29 and 83 years of age, with a mean age of 61+/-10.9 years. VEGF -2578 C>A and VEGF -634 G>C genotype frequencies were similar among patients and controls. Carriers of the 936T-allele were found slightly more frequent among controls (27.2%) than among patients (22.5%), but this difference did not reach statistical significance (P=0.07). Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. We conclude that the investigated polymorphisms are not associated with individual susceptibility to colorectal cancer.

Preservation of nipple-areola complex in breast cancer – a clinicopathological assessment

Skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR), which traditionally includes the nipple-areola complex (NAC), is the modern way of improving the cosmetic and aesthetic outcome of advanced breast cancer surgery. However, with nipple and areola lacking, it fails to simulate the original breast. This study is directed at exploring the possibility of NAC preservation in selected mastectomy patients. A retrospective analysis of the breast specimens of 219 consecutive mastectomy patients was performed after categorising the tumour characteristics on the basis of their TNM staging. The relationship of malignant involvement of the NAC with positive regional lymph nodes (pN), tumour size (T), site, stage and skin involvement by the breast tumour was noted and analysed. Chi-square analysis was performed for different characteristics vis-à-vis NAC involvement. Two-sided lists, wherever possible, had been performed at the 5% level of significance and P values were evaluated. The total frequency of malignant involvement of NAC was 44 (20%) out of 219. The frequency of NAC involvement in stage I and II tumours was found to be 9.38% compared to stage III tumours where it was 30%. The NAC was involved in 4 (2.5%) of 160 patients with peripheral tumours compared with 40 (68%) of 59 patients with tumours located centrally. Only 2 (1.5%) of 130 peripheral tumours bigger than 5 cm had malignant NAC involvement while the number in their central counterparts was much bigger (59%). Not a single breast cancer patient with skin involvement in the peripheral quadrants had any nipple-areola involvement. NAC can be preserved in patients having stage I, II and III diseases with peripheral tumours less than 5 cm in size, irrespective of the nodal status and skin involvement.

The Evaluation of Definitive Radiation Therapy for Patients with Stage II-III Squamous Cell Carcinoma of the Esophagus

Purpose: The aim of this study is to evaluate the outcome of the patients with stage II-III esophageal cancer treated with radiation therapy. Methods: Between 1999 and 2006, 87 patients with squamous cell esophageal carcinoma were treated with radiation therapy (RT) or concurrent chemoradiotherapy (CRT) at Gunma University Hospital. Seventy-four patients were men and 14 patients were women, and the median age was 71 years (range: 48–93 years). According to TNM staging system (UICC, 2002), 29 patients were stage II (IIA: 23, IIB: 6), and 58 patients were stage III. Radiation therapy consisted of 40–46 Gy with anteroposterior opposing field including the primary tumor and positive regional lymphnodes with optimal margins with conventional fraction followed by external beam boost up to 50–70 Gy (median: 64 Gy). Chemotherapy was administered concurrently with radiation therapy to 50 patients, and the 30 patients received the regimen contained cisplatin or nedaplatin (CRT-PT) and the 20 patients received the regimen consisting of docetaxel (CRT-DOC). Results: At the end of this study, there were 27 survivors with a median follow-up period of 20 months (range: 6–85 months). The 2- and 3-year disease specific survival rates (DSS) were 44% and 29% for all 87 patients, 71% and 44% for stage II, and 31% and 22% for stage III. The difference of DSS between the patients with stage II and stage III was statistically significant (P= 0.0016). The CR rate and the 2- and 3-year DSS for the CRT group were 34%, 44%, 29%, respectively, and these results were better than those for the RT group of 24%, 43%, 19%, respectively, however, these differences observed were not statistically significant. The outcomes of the patients with CRT-DOC regimen resulted in almost the same as those of CRT-PT regimen group. Conclusion: Our results revealed that definitive radiation therapy for squamous cell carcinoma of the esophagus is effective. Further investigations of the protocol of radiation therapy technique or chemotherapy are needed to clarify the impact of CRT on prognosis of the patients with this disease.

Androgen deprivation therapy (ADT) for node postive prostate cancer

5061 Background: The role of ADT for men with node positive prostate cancer following radical prostatectomy (RP) is unclear. One randomized trial has shown a survival advantage for men treated with immediate adjuvant (adj) ADT compared treatment at onset of clinical metastases. However, benefit of immediate therapy is less clear in the PSA era when ADT can initiated at the time of biochemical relapse. Methods: We used linked Surveillance, Epidemiology and End Results-Medicare Data to identify a cohort of men who underwent RP between 1991–1999 and were found to have positive regional lymph nodes. We searched Medicare claims to identify men with claims for ADT (hormonal therapy or orchiectomy) within 3 years of diagnosis. We excluded men who received ADT prior to RP. We classified men as receiving adj ADT if they received treatment within 120 days of RP and compared them to men who had not received adj ADT. We used propensity scores to balance potential confounders of receiving adj ADT (age, tumor characteristics, extent of nodal disease, demographics). We used Cox proportional hazard methods to estimate the impact of adj ADT on overall survival (OS) adjusting for propensity score. We conducted a sensitivity analysis using 90, 150, 180 and 365 days as the time limit for adj ADT. Results: 719 men were identified, of whom 190 received adjuvant ADT within 120 days of RP. There was no statistically significant difference in overall survival between the men who did or did not receive adj ADT (HR 0.96 95% CI 0.70–1.32) The results were similar for men who received ADT within 90 and 150 days. However, when the definition of adj ADT was moved to 180 days (HR 1.08 (0.80–1.47)) and 365 days (HR 1.24 (0.92–1.65)) the men receiving adj ADT had a slightly higher risk of death, suggesting some in the adj ADT groups using these later definitions may have received therapy as salvage therapy for progressive disease. Conclusions: This observational study suggests that in the PSA era when men can be started on ADT at the time of biochemical recurrence, overall survival may not be significantly compromised by deferring immediate ADT in men with positive lymph nodes following RP. Further clinical research is needed to better understand which patients are likely to benefit from immediate ADT, and which men can be spared the long term toxicities. [Table: see text]

Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma

Aim The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes. Methods Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months. Results Nodal disease was found in 31 patients, of whom 23 had 1–3 positive regional nodes and 8 had ≥4 positive regional nodes. Univariate analysis revealed that both the location ( p < 0.0001) and the number ( p < 0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor ( p = 0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1–3 positive nodes, whereas all patients with ≥4 positive nodes died of the disease within 29 months of resection ( p = 0.0001). Conclusion The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

Extranodal Extension in Regional Lymph Nodes is Associated With Outcome in Patients With Renal Cell Carcinoma

The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.

Cutaneous Angiosarcoma

To discuss the treatment and outcomes for cutaneous angiosarcoma. Review of the pertinent literature. Cutaneous angiosarcoma is a rare, aggressive malignancy with a poor prognosis. It usually arises in the scalp or face and is locally advanced at presentation. Patients are most often white, male, and elderly. A subset of patients presents with multifocal disease and/or positive regional nodes. Although the optimal treatment is surgery followed by wide-field radiotherapy (RT), the disease is frequently so extensive at diagnosis that it is not completely resectable. Even after optimal local-regional treatment, there is a relatively high likelihood of a local recurrence at the margins of the RT fields. The probability of hematogenous dissemination is relatively high. Limited data suggest that chemotherapy may be useful for palliation with progression-free survival rates ranging from 1 to 5 months. The 5-year local-regional control rates are approximately 40% to 50%, the 5-year distant metastasis-free survival rates range from 20% to 40%, and the 5-year survival rates range from 10% to 30%. Cutaneous angiosarcoma is a rare, aggressive malignancy that is optimally treated with resection and wide-field postoperative RT. The likelihood of local-regional failure is high, as is the risk of distant relapse. Chemotherapy may be useful for short-term palliation.

Introduction of sentinel node biopsy and stage migration of breast cancer

Aim The purpose of this study was to examine in a large population based group of breast cancer patients treated in a regular care setting whether the introduction of the Sentinel Node Biopsy (SNB) led to detection of a higher percentage of patients with positive regional lymph nodes. Methods The study includes 3665 early breast cancer patients, aged 30–85 years, diagnosed in the period 1997-2002 and registered at the Regional Cancer Registry of the Comprehensive Cancer Centre Middle Netherlands. During this period the SNB was introduced. The outcome of staging was compared for groups staged with or without SNB. A logistic regression model was used to adjust for age, calendar period and tumour size. Results Overall a quarter of all patients over the period 1997–2002 underwent a SNB as method of lymphatic staging. The use of SNB clearly increased over time: from 2% in 1998 to 65% in 2002. The percentage node positive patients also rose significantly; before introduction of the SNB 30% of all patients were diagnosed with positive lymph nodes, and after SNB introduction this percentage was 40%. The increase is largely explained by the increase of patients diagnosed with only micrometastases. Adjustment did not change the results. Conclusion In conclusion, introduction of the SNB in early breast cancer led to significant upstaging of breast cancer patients treated in a regular care setting, due to the detection of more micrometastases. Since the relevance of micrometastases for long term survival is not yet known, this upstaging potentially led to over treatment of patients. On the other side, for some patients axillary lymph node dissection was prevented by the SNB procedure, preventing comorbidity.

Radical prostatectomy for clinical T4 prostate cancer

Occasionally, patients with clinical T4 (cT4) prostate cancer undergo surgery. Published data on outcomes after radical prostatectomy (RP) in patients with such advanced stage disease and on the impact of adjuvant radiation therapy (RT) and hormone therapy (HT) are nonexistent. Data from the Surveillance Epidemiology and End Results (SEER) data base were reviewed for the 7-year period from 1995 to 2001. Specifically, data were analyzed for 1093 patients with cT4, lymph node-negative or lymph node-positive, M0 prostate cancer without distant lymph node involvement or a history of other cancer. Using follow-up data through 2002, postdiagnosis survival was examined in 5 treatment groups: radical prostatectomy (RP) either alone or in combination with other therapy, radiation therapy (RT) alone, hormone therapy (HT) alone, RT plus HT, and no treatment (NT). All results were expressed as 1-year, 3-year, and 5-year observed survival and corresponding relative survival. Mortality across treatment categories was compared by using a Cox proportionate hazards model controlling for age, year of diagnosis, race, tumor grade, regional lymph node involvement, clinical tumor extension, and SEER registry. Observed and relative survival rates were lowest among patients who received NT and highest among patients who underwent RP. Adding adjuvant RT or HT to RP conferred no survival benefit. Multivariate survival analyses revealed a significant increase in mortality among HT-only patients and among patients who received NT compared with patients who underwent RP. The differences in survival among treatment types were most pronounced in a relatively small group of patients who had positive regional lymph node extension. In all other patients, the results suggested a modest (but not significant) improvement in survival after RT plus HT. SEER data revealed that patients who underwent RP for cT4 prostate cancer had increased survival compared with patients who received RT alone or HT alone and had a survival comparable to that of patients who received RT plus HT. The benefit of RP appears to be limited to a relatively small subset of patients who have regional lymph node extension.

Sinonasal Undifferentiated Carcinoma

The purpose of this paper is to discuss the treatment and outcomes for patients with sinonasal undifferentiated carcinoma. Review of the pertinent literature. Most series contain a limited number of patients treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up periods for disease-free patients are sometimes relatively short. The majority of patients present with locally advanced tumors; 10% to 30% have clinically positive regional nodes. The risk of local-regional recurrence after treatment is probably 20% to 30% or higher, depending on the extent of disease. The likelihood of distant dissemination is approximately 25% to 30% and the cure rate varies from roughly 20% to 50%. Better outcomes are observed in patients treated with craniofacial resection combined with pre- or postoperative RT alone or with adjuvant chemotherapy. This is probably due, in part, to selection bias. Patients with incompletely resectable tumors are best treated with definitive RT and adjuvant chemotherapy. The optimal treatment is craniofacial resection combined with adjuvant RT alone or with chemotherapy. The risk of relapse is relatively high and the probability of cure is modest. Patients with incompletely resectable tumors may sometimes be cured with definitive chemoradiation.

Evaluation of the results of oesophagectomy for oesophageal cancer

The long-term results of standard techniques of oesophagectomy were examined in 127 patients with squamous cell carcinoma of the oesophagus. A near-total oesophagectomy with a cervical anastomosis was performed in 93 patients and an oesophagogastrectomy with an intrathoracic anastomosis was carried out in 34 patients. One hundred and eight patients had a curative oesophagectomy and 19 patients had a palliative resection. Eight patients received radiotherapy to the tumour bed. There were 15 deaths in hospital and the overall 5-year survival rate including perioperative deaths was 13.2 per cent. Survival was adversely affected by incomplete excision of macroscopic tumour (P less than 0.001), positive regional lymph nodes (P less than 0.05) and distant lymphatic metastases (P less than 0.02). The 5-year survival rate of patients with tumour invasion beyond the oesophageal wall (T3) and negative nodes was 20 per cent. Postoperative irradiation had no effect on the survival of patients with gross residual tumour. Complete clearance of microscopic tumour was achieved in 50 per cent of patients with T3 tumours and this group did not benefit from adjuvant radiotherapy. Survival in patients undergoing curative oesophagectomy with residual microscopic tumour, however, was significantly improved by irradiation of the tumour bed (P less than 0.01). These results suggest that the survival of patients can be increased significantly by the excision of all gross tumour and by identification of those who will benefit from local radiotherapy.

Isolated seminal vesicle invasion imparts better outcomes after radical retropubic prostatectomy for clinically localized prostate cancer: Prognostic stratification of pt3b disease by nodal and margin status

Objectives To examine the survival differences in men with seminal vesicle invasion (SVI) according to surgical margin (SM) and nodal (N) status to characterize the influence of isolated SVI on disease progression after radical retropubic prostatectomy for clinically localized prostate cancer. Methods We reviewed the records of 941 men who underwent radical retropubic prostatectomy for clinically localized prostate cancer between 1984 and 2002. Three groups with evidence of SVI (SM−/N−, SM+/N−, and N+) were analyzed to identify differences in age, preoperative prostate-specific antigen (PSA) level, biopsy Gleason score, surgical Gleason score, time to PSA progression, follow-up time, and cancer-specific and overall survival. Kaplan-Meier estimates and univariate and multivariate calculations were generated to examine differences in biochemical-free survival. Results Of 941 patients, 87 were identified with SVI; of these, 28 (32.2%) were SM−/N−, 35 (40.2%) were SM+/N−, and 24 (27.6%) were N+. The median follow-up for all patients was 70 months. The 5-year biochemical progression-free rate for SM−/N−, SM+/N−, and N+ patients was 71.9%, 36.6%, and 25.9%, respectively. The median time to PSA progression for SM−/N−, SM+/N−, and N+ patients was 26, 16, and 6 months, respectively. The clinical stage, pretreatment PSA level, and margin and node status were statistically predictive ( P <0.05) on univariate analyses; however, only positive margin status approached statistical significance on multivariate analysis ( P = 0.06). The overall and cancer-specific 5-year survival rates for SM−/N−, SM+/N−, and N+ patients were 89% and 100%, 79% and 97%, and 78% and 86%, respectively. Conclusions Isolated SVI is associated with lower rates of, and longer intervals to, biochemical failure compared with SVI with positive margins and/or regional lymph node involvement.

Safety analysis of docetaxel (T) and doxorubicin (A) followed by sequential capecitabine (X) as adjuvant chemotherapy of patients with node-positive operable breast cancer (BC)

811 Background: T, A, and X have been shown to be very active drugs for the treatment of BC. Sequential administration of these chemotherapy agents has improved the toxicity profile versus concurrent administration. This study evaluated the safety profile of AT followed by sequential X in the adjuvant setting in patients with node-positive BC. Methods: Patients with histological diagnosis of stage II-III BC, positive regional lymph nodes, completed BC surgery, age ≥18 years, ECOG PS ≤ 2, and adequate bone marrow, renal, hepatic and cardiac function were included in the study. Prior chemotherapy, hormone therapy, and radiotherapy for BC were not allowed. Treatment: 6 courses of T 75 mg/m2 iv D1 and A 50 mg/m2 iv D1, every 21 days followed by 6 courses of X 2500 mg/m2/day po D1–14 and Vitamin B6 300 mg bid po D1–21 every 21- days. Results: Ninety-one of the 115 patients enrolled were included in this interim analysis. Median age:47 years (range 28–73), ECOG PS 0–1 100%, hormone receptor status was 64% ER/PR+, 13% ER+ and 4% PR+. Ductal infiltrating carcinoma was observed in 91% of patients. Median number of positive regional lymph nodes was 3 (maximum 30). Surgery was lumpectomy in 33% and mastectomy in 67% of patients. A total of 471 cycles of AT (median 6 per patient, range 1–6) and 243 cycles of X (median 4.5, range 1–6) were administered. Median RDIs were 99% for A, 99% for T, and 91% for X. All patients were evaluable for toxicity. During AT treatment, the main grade 3–4 toxicities per cycle were neutropenia (3%), leukopenia (2%), constipation (1%), amenorrhea (1%) and diarrhea (0.4%). There were 9 episodes of febrile neutropenia in 8 patients. During X treatment, the main grade 3–4 toxicities per cycle were neutropenia (1%), amenorrhea (3%), cutaneous toxicity (1%), hand-foot syndrome (1%) and stomatitis (0.4%). Grade 1–2 hand-foot syndrome occurred in 21% of cycles. With median follow-up of 6.7 months, no relapses were seen. Treatment of the last patient will be completed by Easter 2005, and full toxicity data on all 115 patients will be presented. Conclusions: AT followed by sequential X as adjuvant treatment of node-positive BC patients is a well-tolerated regimen. No significant financial relationships to disclose.

Early ipsilateral breast tumor recurrences after breast conservation affect survival: An analysis of the National Cancer Institute randomized trial

To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.