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Donald L Morton

Publications and source records attributed to Donald L Morton.

71 records · Page 4Linked to original sources
PubMed2002

Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma.

BACKGROUND: We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence. METHODS: From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guérin (BCG). PACV Delayed-type hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death. RESULTS: Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P =.0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P =.0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P =.0178). CONCLUSIONS: Reinduction vaccine regimen can enhance immune responses in previously immunized patients and is associated with prolonged survival after recurrence in patients receiving the same active specific immunotherapy.

Adolescent↗
PubMed2002

Serum TA90 immune complex assay can predict outcome after resection of thick (> or =4 mm) primary melanoma and sentinel lymphadenectomy.

BACKGROUND: We hypothesized that the postoperative serum level of TA90-IC, an immune complex of a 90-kDa tumor-associated antigen and its antibody, might have a significant correlation with recurrence and survival in patients with thick primary melanomas. METHODS: We used our prospective melanoma database to identify all patients who underwent wide local excision and sentinel lymphadenectomy for primary melanomas > or =4 mm and from whom sera had been collected and cryopreserved within 6 months after surgery. These sera were analyzed in a blinded fashion for TA90-IC status by using our double-determinant enzyme-linked immunosorbent assay. Results were correlated with disease-free survival (DFS) and overall survival (OS). Standard prognostic factors for melanoma were then compared with TA90-IC status for the prediction of DFS and OS. RESULTS: The sensitivity and specificity of the TA90-IC assay for predicting recurrence were 70% and 85%, respectively. Five-year DFS and OS rates were higher for the TA90-IC-negative group than the positive group. The differences in DFS and OS between the TA90-IC-negative and -positive groups were significant. At a median follow-up of 25 months, multivariate analysis identified postoperative TA90-IC status and sex as significant predictors of DFS. TA90-IC status was the only independent prognostic factor with multivariate analysis. CONCLUSIONS: TA90-IC status after resection of thick primary melanoma accurately predicts outcome. A positive postoperative TA90-IC level might affect a decision regarding adjuvant therapy, regardless of regional nodal status.

Adult↗
PubMed2002

Systemic irinotecan and regional floxuridine after hepatic cytoreduction in 185 patients with unresectable colorectal cancer metastases.

BACKGROUND: This study evaluated our 7-year experience treating unresectable colorectal cancer (CRC) hepatic metastases refractory to systemic 5-fluorouracil. METHODS: A total of 185 patients with unresectable 5-fluorouracil-resistant CRC hepatic metastases underwent surgical cytoreduction. Postoperatively patients received either hepatic arterial floxuridine (FUDR) and systemic irinotecan as part of a phase II trial or no further treatment. RESULTS: Of the 185 patients undergoing surgical cytoreduction, 71 patients received adjuvant irinotecan/FUDR. There were no appreciable differences in synchronous or metachronous lesions or the median number or size of lesions between treatment groups. At a median follow-up of 20 months, there were fewer recurrences in patients treated with postoperative irinotecan/FUDR compared with untreated patients for both hepatic and extrahepatic recurrences. Progression-free and overall survival were longer for patients who received irinotecan/FUDR compared with patients who did not receive adjuvant therapy. The 2-year survival rate was significantly better for patients receiving adjuvant therapy compared with patients receiving no additional treatment. Predictors of improved survival included a preoperative carcinoembryonic antigen level <100 ng/dl, >30% postoperative reduction in carcinoembryonic antigen level, and adjuvant therapy. CONCLUSIONS: Combined therapy with irinotecan/FUDR may improve the results of surgical cytoreduction for unresectable CRC hepatic metastases.

Adenocarcinoma↗
PubMed2002

Prognostic implications of thick (>or=4-mm) melanoma in the era of intraoperative lymphatic mapping and sentinel lymphadenectomy.

BACKGROUND: Lymphatic mapping/sentinel lymphadenectomy (LM/SL) has become a routine part of our treatment algorithm for primary melanoma, yet its role in the management of thick (>or=4-mm) lesions is unknown. METHODS: One hundred twenty-one patients with thick primaries underwent LM/SL at our institute. Survival curves were constructed from Kaplan-Meier estimates and analyzed by Cox proportional hazards methods. RESULTS: Sixty-three percent of patients were men, median age 54 years. The primary tumor sites were trunk (46%), extremities (32%), and head and neck (21%). Primary thickness ranged from 4 to 15 mm (median, 6.0 mm). Forty-five percent of primary tumors were ulcerated. Thirty-five percent of patients had tumor-positive dissections. Median follow-up was 31 months. The overall 5-year survival was no different (P =.726) for ulcerated and nonulcerated lesions. There was no difference (P =.159) in overall survival after tumor-negative (60% +/- 7%) and tumor-positive (50% +/- 10%) dissections. The 5-year disease-free survival was significantly (P =.012) lower in patients with tumor-positive (34% +/- 9%) than tumor-negative (47% +/- 7%) dissections. CONCLUSIONS: Although LM/SL has become a popular technique for staging the regional lymph nodes in early-stage melanoma, our results suggest that sentinel node status is predictive of disease-free survival for thick primary tumors but is not yet reflective of overall survival. The role of LM/SL for patients with thick primary tumors is not clearly defined.

Adult↗
PubMed2002

Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM.

Cryosurgical ablation (CSA) of tumors induces disruptive necrosis. Necrosis may release tumor gangliosides into circulation and they may augment serum antiganglioside antibodies depending on the nature of gangliosides released. The hypothesis is tested by determining the level of serum total gangliosides (STG) and their antibody titers in the sera of colon cancer patients with cryoablated liver tumors. As controls, we examined the sera of patients who underwent radiofrequency ablation (RFA) and regular surgery (RS), none of which cause disruptive necrosis. The STG level (expressed as lipid-bound sialic acids, LBSA) is higher (p(2)<0.001) in 35 patients (stage IV) than in 38 healthy case-controls (median 23.48 mg/dL, Q-range 7.1 vs 16.04 mg/dL, Q-range 4.5). The mean STG level increased significantly to 31.2+/-6.0mg/dL (p(2)<0.03) after CSA. Concomitantly, the IgM titer against colon cancer-associated gangliosides (GM(2), GD(1a), GT(1b)), increased significantly, but no increase was observed against normal tissue gangliosides (GM(3) or GM(1)). Also after RFA and RS, no such increase was observed either in the level of STG or in IgM titer against tumor gangliosides. The results suggest that CSA-induced necrosis might have acted as an adjuvant, because purified gangliosides without exogenous adjuvants even after repeated immunization failed to elicit antibody response. The post-CSA decline in the STG level correlated with the increase in the antibodies, suggesting a homeostatic role of the antibodies.

Adenocarcinoma↗
PubMed2002

Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes.

OBJECTIVE: To determine whether adjuvant postoperative active specific immunotherapy with a therapeutic polyvalent vaccine (PV) called Canvaxin can prolong survival following complete resection of melanoma metastatic to regional nodes (American Joint Committee on Cancer [AJCC] stage III melanoma). SUMMARY BACKGROUND DATA: Despite complete lymphadenectomy, 5-year overall survival (OS) for patients with melanoma metastatic to regional lymph nodes is only 20% to 50%, depending on the number of tumor-involved nodes. In 1984, the authors began phase II trials of Canvaxin PV as postsurgical adjuvant therapy for AJCC stage III melanoma. METHODS: Patients who received PV between 1984 and 1998 were compared with patients who did not receive PV postsurgical therapy between 1971 and 1998. The seven covariates recently defined by the AJCC Melanoma Staging Committee (number of metastatic nodes, palpable status, ulceration, age, primary site, pT stage, and gender) were included by Cox regression in a multivariate model of OS. A computerized program matched PV and non-PV patients by these covariates. RESULTS: Of 2,602 patients who underwent complete lymphadenectomy for AJCC stage III melanoma with regional nodal metastases and were followed up by the same team of oncologists between 1971 and 1998, 935 received PV and 1,667 did not. Median OS and 5-year OS were significantly higher in PV than non-PV patients (56.4 vs. 31.9 months and 49% vs. 37%, respectively; P =.0001). When the non-PV patients were matched by the four most significant covariates, 447 matched pairs were formed between patients seen before or after January 1, 1985, and the OS was not different between the two time periods ( P=.789). However, when the PV patients were matched with non-PV patients by six covariates forming 739 pairs, the PV patients survived longer ( P=.0001). Detailed analysis of the 1,505 patients who were seen or who began vaccine therapy within 4 months after lymphadenectomy, and who had more complete data on the seven prognostic covariates showed that median OS and 5-year OS were higher in 445 PV patients than in 1,060 non-PV patients: 70.4 versus 31 months and 52% versus 37%, respectively (P =.0001). Multivariate Cox regression analysis identified six significant prognostic factors: number of metastatic nodes, size of metastatic nodes, pT stage, ulceration, age, and PV therapy. PV therapy reduced the relative risk of death to 0.64 (95% confidence interval, 0.55-0.76) ( P=.0001); sex and site of primary were of borderline significance. CONCLUSIONS: This large single-institution study independently confirmed the significance of prognostic covariates in the new AJCC staging system. By using modern statistical methods that controlled for all known prognostic factors, it also demonstrated PV's ability to significantly enhance OS. A multicenter phase III randomized trial is underway to validate the efficacy of PV as a postsurgical adjuvant.

Aged↗
PubMed2002

A novel lymphatic mapping technique to improve localization and staging of early colon cancer during laparoscopic colectomy.

Encouraging results from our previous studies of sentinel lymph node (SLN) mapping in colorectal cancer (CRC) prompted investigation of its feasibility and accuracy during laparoscopic colectomy for early CRC. Between 1996 and 2000, 14 patients with clinically localized colorectal neoplasms underwent colonoscopic tattooing of the primary site and SLN mapping. In each case 0.5 to 1 cm3 of isosulfan blue dye was injected submucosally via the colonoscope. The blue-stained lymphatics were visualized through the laparoscope and followed to the SLN, which was marked with a clip, and laparoscopic colectomy was completed in the routine fashion. All lymph nodes were examined by hematoxylin and eosin (H&E) staining; in addition each SLN was subjected to focused examination by multisectioning and immunohistochemical staining using cytokeratin antibody. In all 14 patients the primary neoplasm and an SLN were identified laparoscopically. An average of 13.5 total lymph nodes and 1.7 SLNs per patient were identified. The SLN correctly reflected the tumor status of the nodal basin in 93 per cent of the cases. In four cases with unexpected lymphatic drainage, the extent of mesenteric resection was altered. In two cases (14%), nodal involvement was micrometastatic, confined to an SLN, and identified only by immunohistochemical staining. Lymphatic mapping caused no complications and added only 10 to 15 minutes to the overall operative time. Comparison of results in this group with results for a matched group of 14 patients undergoing SLN mapping during open colon resection showed that the laparoscopic technique had similar rates of accuracy and success. These preliminary findings indicate that colonoscopic/laparoscopic SLN mapping during laparoscopic colon resection is a feasible and technically simple means of identifying the primary colorectal neoplasm and its SLN. Focused pathologic examination of this node can upstage CRC and thereby may improve selection of patients for adjuvant chemotherapy.

Adult↗
PubMedDate not supplied

Preoperative serum TA90-IC as an adjunct to serum CA 19-9 in the diagnosis of pancreatic malignancy: a pilot study.

PURPOSE: Because TA90, a 90-kDa immunogenic tumor-associated antigen, is expressed by pancreatic cancer cells, we hypothesized that the serum level of its immune complex with IgG (TA90-IC) might be a useful marker for diagnosis of pancreatic malignancy. We also wanted to compare TA90-IC with CA 19-9 in the diagnosis of pancreatic cancer. METHODS: We undertook a retrospective study of prospectively collected sera from patients with histopathologically proven pancreatic malignancies. Patient sera were analyzed for TA90-IC and CA 19-9. Sera of sex-matched and age-matched healthy volunteers (controls) were analyzed for TA90-IC. The study was conducted at a tertiary medical center. Twenty-one patients with pancreatic malignancies and 29 controls, from whom sera had been obtained and cryopreserved, were included. A positive TA90-IC level was defined as an optical density >/= 0.410 at 405 nm following an enzyme-linked immunosorbent assay based on a murine monoclonal antibody. CA 19-9 levels were determined by immunoradiometric assay performed at outside laboratories (normal range, 0 to 37 U/mL). RESULTS: Of the 21 patients, 14 had positive TA90-IC levels and 18 had increased CA 19-9 levels (67% vs 86%; p = 0.157). The TA90-IC levels were significantly higher in the cancer group than in the control group (p = 0.0003). Of the 3 patients with normal CA 19-9 levels, 2 had positive TA90-IC levels. The combination of both markers identified 95% of patients with pancreatic malignancy, a significantly higher diagnostic rate than that of either marker alone (p = 0.014). TA90-IC sensitivity was higher for stage II and III disease than for stage IV disease (82% vs 50%). CONCLUSIONS: TA90-IC assay may improve the prediction of pancreatic malignancy when used in combination with CA 19-9 levels. Because TA90-IC appears to have improved diagnostic accuracy with smaller tumor burden, the role of TA90-IC as an adjunct to CA 19-9 in screening and monitoring progression of early disease warrants further investigation.

Journal Article↗
PubMedDate not supplied

One hundred consecutive cases of sentinel lymph node mapping in early colorectal carcinoma: detection of missed micrometastases.

Almost one third of patients with "node-negative" colorectal carcinoma (CRC) develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. We have coupled sentinel lymph node mapping and a focused pathologic examination to detect occult nodal micrometastases in CRC. Since 1996, sentinel lymph node mapping has been performed in 100 consecutive patients undergoing colectomy for CRC. Peritumoral injection of 0.5 to 1.0 ml of isosulfan blue dye was performed to demonstrate the sentinel node(s). All lymph nodes in the resection specimen were examined by routine hematoxylin and eosin staining. In addition, a focused examination of multiple sections of the sentinel nodes was performed using both hematoxylin and eosin and cytokeratin immunohistochemical analysis (CK-IHC). Overall, lymphatic mapping successfully demonstrated one to four sentinel lymph nodes in 97 (97%) of 100 patients. These sentinel nodes accurately reflected the status of the nodal basin in 92 (95%) of 97 patients. All five of the false negative cases occurred in T3/T4 tumors, and three of the five occurred during the first 30 cases in the experience. Unexpected lymphatic drainage was encountered in eight patients (8%) and altered the operative approach. Twenty-six patients were node positive by routine hematoxylin and eosin staining. Of the remaining 74 patients with hematoxylin and eosin-negative nodes, an additional 18 patients (24%) were upstaged by identification of occult nodal micrometastases that were missed on routine hematoxylin and eosin staining but detected on multiple sections (n = 5) or by CK-IHC (n = 13). The sentinel lymph nodes were the only positive nodes in 19 cases. Sentinel lymph node mapping may be performed in CRC with a high degree of success and accuracy. A focused pathologic examination of the sentinel node detects micrometastatic disease that is missed by conventional techniques in a significant proportion of patients with early CRC. Further studies are necessary to elucidate the clinical relevance of these micrometastases.

Adult↗
PubMedDate not supplied

Combination probe and dye-directed lymphatic mapping detects micrometastases in early colorectal cancer.

Nodal metastasis is the single most important prognostic factor in early colorectal cancer (CRC). Lymphatic mapping can identify sentinel nodes for focused histopathologic examination and thereby improve the nodal staging of CRC; however, the optimal technique for identifying sentinel nodes in CRC is unclear. We hypothesized that a combination of radiotracer and blue dye would more accurately identify tumor-positive sentinel nodes than blue dye alone. Lymphatic mapping was performed in 48 consecutive patients undergoing resection for CRC and in two original patients who underwent sentinel node mapping in 1996. Prior to resection, 1% vital blue dye and radiotracer were injected around the tumor in the subserosal layer. Nodes were designated as sentinel by blue coloration and/or radioactivity. Lymphatic mapping identified at least one sentinel node in 49 patients. Focused examination of multiple sentinel node sections by means of hematoxylin and eosin and immunohistochemical analysis showed that sentinel nodes accurately predicted the status of the nodal basin in 93.8% (46 of 49) of patients. Of the 19 patients with nodal metastases, 11 had macrometastases (>.2 mm), three had micrometastases (between 2 mm and 0.2 mm), and five had isolated tumor cells or clusters (<.2 mm) identified by immunohistochemical analysis only. Patients had significantly fewer blue/radioactive ("hot") nodes than blue-only nodes (1.38 vs. 2.48 per patient; P = 0.0001). It is important to note that nodal metastases were more common in blue/hot nodes than in blue-only nodes (27.3% [19 of 68] vs. 8.8% [11 of 124]; P = 0.005). Dual-agent lymphatic mapping more accurately identifies sentinel node metastases than blue dye alone. In addition, this technique allows a more focused histopathologic examination of these nodes, in conjunction with the revised American Joint Committee on Cancer guidelines, and thereby offers the potential for significant upstaging of CRC.

Aged↗
PubMedDate not supplied

Serum total ganglioside level correlates with clinical course in melanoma patients after immunotherapy with therapeutic cancer vaccine.

The authors tested the hypothesis that the therapeutic destruction of residual tumors may be reflected in the level of serum total gangliosides (sTG). The sTG level was evaluated in 17 patients with in-transit melanoma and 70 patients with resected regional node metastasis, who have received a polyvalent therapeutic melanoma cell vaccine. The treatment response was determined by regression of in-transit metastases or by overall survival after resection. sTG levels were measured, blinded, before and after immunotherapy. The mean sTG level of the in-transit melanoma patients increased from 18.57 +/- 3.18 mg/dL pretreatment to 23.7 +/- 5.5 mg/dL between weeks 2 and 16 after initiation of treatment (p(2) < 0.0001). By week 24, the level had returned to its prevaccine level in the seven clinical responders (18.1 +/- 2.3 mg/dL vs. 20.4 +/- 3.2 mg/dL; p(2) < 0.050) but remained higher than its prevaccine level in the 10 nonresponders (23.3 +/- 5.1 mg/dl vs. 17.2 +/- 2.7 mg/dL). Similarly, the sTG level of the patients with nodal metastases increased between weeks 2 and 16 after the first vaccine treatment; by week 24, it had returned to pretreatment level in patients who survived more than 56 weeks but remained significantly elevated (p(2) < 0.01) in patients who survived less than 56 weeks. The sTG level increased between weeks 2 and 16 in all vaccine recipients and returned to prevaccine level by week 24 in all who showed measurable regression of in-transit melanoma (7 of 17 patients) or improved overall survival (53 of 70 patients). The data suggest that sTG level could be a potential tool for assessing the response to immunotherapy in melanoma patients by week 24.

Adult↗
PubMedDate not supplied

Serum total gangliosides and TA90-IC levels: novel immunologic markers in colorectal cancer.

BACKGROUND: Because of the challenge in defining prognostic markers predictive of recurrence or progression, carcinoembryonic antigen (CEA) remains the most frequently used marker in colorectal cancer, despite its low sensitivity. We hypothesized that TA90-IC status and serum ganglioside levels might be useful markers and might be of prognostic significance in colorectal cancer. METHODS: Serum samples from 68 patients undergoing surgical treatment for histologically proven colorectal cancer were analyzed for the presence of CEA, serum gangliosides, and TA90-IC. Forty-one patients had node-negative disease, whereas 27 patients had limited metastatic disease. The intent was curative resection, even for patients with metastatic disease. Cryopreserved serum specimens were analyzed in a blinded fashion for total serum ganglioside levels (by an assay that detects lipid-associated sialic acids), for CEA, and for TA90-IC (by a murine monoclonal antibody-based enzyme-linked immunosorbent assay). A positive value for TA90-IC levels was defined as an optical density (OD) of more than 0.410 at 405 nm. RESULTS: Serum ganglioside levels were elevated more frequently than CEA concentrations (84% vs 44%). The combination of serum ganglioside and CEA values was more sensitive (88%) than CEA value alone (44%) in identifying patients with early-stage colorectal cancer. TA90-IC levels were elevated more frequently than CEA concentrations (56% vs 32%). The combination of TA90-IC and CEA values was more sensitive (72%) than CEA value alone (32%) in identifying patients with advanced-stage colorectal cancer. At an enzyme-linked immunosorbent assay cutoff level of 0.410, 15 (56%) patients had positive TA90-IC values. Fourteen patients alive with residual disease had a median OD TA90-IC level of 0.879, and only three patients had levels below the OD cutoff value of 0.410. Thirteen patients with no evidence of disease had a median level of 0.277, and only four patients had OD levels > or = 0.410. TA90-IC was significantly higher in the alive with residual disease patients than those rendered no evidence of disease (P = 0.02). CONCLUSIONS: We speculate that a multiple-marker analysis that combines CEA values with serum ganglioside and TA90-IC values may be more sensitive than CEA value alone for detecting colorectal cancer. The potential prognostic significance of TA90-IC status in advanced disease warrants further investigation.

Adult↗
PubMedDate not supplied

Serum anti-ganglioside IgM antibodies in soft tissue sarcoma: clinical prognostic implications.

PURPOSE: Gangliosides are tumor-associated antigens with many biologic functions, including complex interactions with cytokines and other modulators of the immune system. Serum total ganglioside level may be an ideal surrogate marker to predict tumor burden and response to treatment. Antibodies produced against tumor gangliosides may help predict survival. The purpose of this study is to determine whether the serum total ganglioside levels might predict the tumor burden in patients with soft tissue sarcoma, and whether the augmented anti-ganglioside immunoglobulin M (IgM) response might reflect the clinical outcome of these patients. METHODS: Serum TG levels were measured in the cryopreserved sera by estimating lipid-associated sialic acids from 97 patients before surgical resection of soft tissue sarcoma and from 39 age- and gender-matched healthy volunteers. All sera were analyzed for IgM titers (expressed natural log) by enzyme-linked immunosorbent assay against eight gangliosides (GM1, GM2, GM3, GD3, GD2, GD1a, GD1b, and GT1b). Cox regression was used for univariate and multivariate analyses of the variables affecting progression-free and overall survival. RESULTS: Serum TG levels were higher in soft tissue sarcoma patients than in healthy individuals (21.8 + 7.7 vs 16.1 + 2.7 mg/dL; P = 0.001). Larger tumors, high histologic grade, and more advanced stage of disease correlated with higher serum total ganglioside levels (P < 0.05). Anti-ganglioside titers to GM3, GD2, and GT1b were significantly higher in patients with soft tissue sarcoma, whereas anti-GD1a and GD1b titers were significantly higher in healthy subjects. The titers of antibodies against GM1, GM2, and GD3 in patients with soft tissue sarcoma were comparable to those of the healthy individuals. When compared with healthy controls, patients with low-grade tumors had higher titers of anti-GT1b, anti-GM3, and anti-GD2 antibodies, and patients with high-grade tumors had higher titers of anti-GT1b and anti-GD2 antibodies. These data suggest that the predominant gangliosides expressed by sarcomas may include GT1b and GD2. In addition, low-grade tumors may express an immunogenic species of GM3. On both univariate and multivariate analyses, augmented anti-GD1a IgM titers, age > 50 years, and retroperitoneal location were predictive of decreased overall survival, whereas augmented anti-GT1b titers were predictive of improved overall survival. CONCLUSIONS: Serum TG level may be a useful marker of tumor burden and response to treatment for soft tissue sarcoma. Anti-GD1a and anti-GT1b IgM titers predicted survival and may be of therapeutic and prognostic value in the management of soft tissue sarcoma.

Adolescent↗
PubMedDate not supplied

Can surgical therapy alone achieve long-term cure of melanoma metastatic to regional nodes?

BACKGROUND: Anecdotal reports of melanoma recurrence 15 years after complete lymphadenectomy have led to claims that the onset of nodal metastasis invariably signals systemic metastases and a terminal diagnosis. Few series in the literature are able to refute this assertion. We therefore examined rates of long-term (> 15-25 years) survival for patients with regional (nodal) melanoma. PATIENTS AND METHODS: We performed an analysis of patients with American Joint Committee on Cancer stage III melanoma entered into a prospective database for the last 30 years. All patients were seen at the treating institution within 4 months of their diagnosis and monitored thereafter. All patients underwent complete lymphadenectomy. Patients receiving melanoma vaccines were excluded. Statistical comparisons used Chi-square analysis and the log-rank test. RESULTS: At a maximum follow up of 386 months (32 years) for the population of 1422 patients, rates of 15-, 20-, and 25-year melanoma-specific survival were 36% +/- 1%, 35% +/- 1%, and 35% +/- 1%, respectively. When patients were stratified by clinical status of regional lymph nodes, survival rates were significantly lower (P = 0.001) if nodes were palpable. The number of tumor-positive nodes (P < 0.0001), the pathological primary tumor stage (P = 0.005), age (P = 0.0001), and gender (P = 0.002) also were significantly related to long-term survival. DISCUSSION: Long-term survivors of melanoma metastatic to regional lymph nodes are not uncommon, and the extremely low rate of recurrence beyond 15 years suggests that this disease-free interval is usually synonymous with cure. Although some risk factors decrease the likelihood of long-term survival, the high overall rates of extended survival in all risk groups clearly support surgical management as the primary treatment for regional metastatic melanoma.

Female↗
PubMedDate not supplied

An evidence-based staging system for cutaneous melanoma.

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.

Databases, Factual↗