Melanoma of unknown primary origin: A population-based study in the Netherlands

AimFew population-based studies have been published on melanoma of unknown primary origin (MUP). This study’s aim is to describe characteristics and survival of MUP patients in the Netherlands, based on nationwide data from the Netherlands Cancer Registry (NCR).MethodsPatient and tumour characteristics of MUP patients were retrieved from the NCR. Subgroups were made according to metastatic site: nodal or distant. Survival rates were calculated using the Kaplan–Meier method. To obtain a better insight in the composition and prognosis of the MUP group, the survival was compared to that of patients with melanoma of a known primary origin (MKP), tumour-node-metastasis (TNM) stage III and IV.ResultsOf all 33,181 melanoma patients diagnosed between 2003 and 2009, 2.6% (n = 857) were diagnosed with MUP. MUP patients with nodal metastases had a similar survival as MKP stage III with macroscopic nodal involvement. After stratification according to the number of involved lymph nodes, the survival of patients with nodal metastases with one involved lymph node was not significantly different between MUP and MKP. The survival of MUP patients with two or more involved lymph nodes was slightly worse than that of MKP stage III patients with macroscopic nodal involvement with two or more involved lymph nodes. MUP patients with distant metastases had a similar survival as MKP stage IV. After stratification according to number of metastatic sites and metastatic site category, the survival in MKP stage IV patients with (sub)cutaneous metastases was slightly worse than MUP distant patients with (sub)cutaneous metastases.ConclusionsThe results of this study imply that MUP patients form a heterogeneous group, and that MUP patients with nodal metastases could be classified as stage III melanoma with macroscopic nodal involvement, and MUP patients with distant metastases as stage IV melanoma.     

Melanoma with unknown primary: report and analysis of 24 patients

In the literature, there are some papers reporting on patients with metastatic melanoma from an unknown primary lesion (MUP). The pathogenesis of this phenomenon and the prognosis of these patients are still debatable. Therefore, we reviewed our casistics on MUP patients. We identified 24 MUP patients out of all patients registered into a melanoma database from June 1996 to June 2011. The incidence was 1.4?%. We compared the survival rate of all patients with MUP stage III-IV with all patients with metastatic melanoma known primary (MMKP) stage III-IV observing a clear survival improvement for MUP patients in front of MMKP patients (p?相似文献   

Patients undergoing lymphadenectomy for stage III melanomas of known or unknown primary site do not differ in outcome

The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma‐specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five‐year adjusted melanoma‐specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.     

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.     

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

BACKGROUND: In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient. METHODS: In 263 consecutive patients with proven American Joint Committee on Cancer Stages I and II cutaneous melanoma, the triple technique SLN procedure was used, i.e., preoperative visualization of the lymph channels from the initial site of the melanoma toward the SLN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and lymph nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabeled lymph nodes. Median follow-up time was 48 months (range, 36-84 months). Multivariate logistic regression analysis was performed to examine the influence of the SLN status and several other prognostic factors on a minimum 3-year disease free survival. RESULTS: In 20% of patients, the SLN proved to be tumor positive. For SLN negative patients, the 5-year disease free survival rate was 91% (+/- 2.4%), and for SLN positive patients it was 49% (+/- 9%). Five variables showed a strong and statistically significant independent prognostic association with outcome, i.e., SLN status (P = 0.0007), thickness of primary melanoma (1.01-2.0 mm; P = 0.04), ulceration (P = 0.05), and lymphatic invasion (P = 0.01) of primary melanoma, and age (40-50 years; P = 0.01). CONCLUSIONS: The SLN status-along with Breslow thickness, ulceration, lymphatic invasion, and age--seems to have strong additional value in predicting a minimum 3-year disease free period after the SLN procedure. Patients with a positive SLN have a poorer prognosis than those with a negative SLN.     

Sentinel lymph node biopsy to stage patients with cutaneous melanoma at the National Cancer Institute of Naples. Results from 240 sentinel node biopsies

AIMS AND BACKGROUND: The presence of lymph node metastases in patients with cutaneous melanoma represents the basis for correct therapy planning and is the most powerful prognostic factor to evaluate overall survival at diagnosis. METHODS AND STUDY DESIGN: Since 1992, when Dr. Morton published his first experience, the sentinel lymph node (SLN) biopsy technique seems to have resolved this matter by correctly staging patients. We analyzed our data from 240 SLN biopsies performed in the last five years at the National Cancer Institute of Naples, evaluating the total identification rate and the nodal recurrence rate, and compared them with the preliminary data of the MSLT (melanoma sentinel lymph node trial). RESULTS: Of all SLNs evaluated 18.5% were micrometastatic and 14% were identified by immunohistochemical staining. Forty-one patients had metastatic SLNs and nodal dissection of the positive basins revealed no other tumor-positive lymph nodes in more than 80% of them. All patients with a Breslow thickness of less than 2 mm had micrometastases only in the SLN, while with increasing thickness two, three or more positive nodes were found. Among SLN-negative patients nine (4%) developed lymph node recurrence in the previously treated basin and were therefore considered as false negative SLN biopsies. CONCLUSIONS: The prognostic value of SLN biopsy needs to be confirmed by the final results of the MSLT evaluating the therapeutic use of this procedure in patients with a Breslow thickness of less than 2 mm and its possible impact on the course of the disease.     

Lymph node metastasis in intrahepatic cholangiocarcinoma

BACKGROUND: Lymph node metastasis is a significant prognostic factor in intrahepatic cholangiocarcinoma. This study was aimed at investigating lymph node metastasis in intrahepatic cholangiocarcinoma and to examine whether the extent of metastasis affects outcomes after surgery. METHODS: From 1980 through 1996, 70 patients with intrahepatic cholangiocarcinoma underwent hepatectomy, with a 50% curative resection rate. Lymph node dissection was performed in 51 patients, and the presence of lymph node metastasis was examined microscopically. The metastatic nodes were divided into groups N1, N2 or N3 using the classification proposed by the Liver Cancer Study Group of Japan. RESULTS: Twenty-three patients had lymph node metastasis. Metastasis was to N1 nodes in 10 patients, to N2 nodes in nine patients and to N3 nodes in four patients. Nineteen patients had metastatic nodes in the hepatoduodenal ligament, which was the most common metastatic site regardless of tumor location. The five-year survival rate in patients with lymph node metastasis (0%) was significantly lower (p < 0.0001) than that in patients without lymph node metastasis (51 %); however, five-year survival rates did not differ between patients with metastases to N1, N2 and N3 nodes. CONCLUSIONS: Lymph nodes in the hepatoduodenal ligament may be sentinel nodes for intrahepatic cholangiocarcinoma, and outcomes after surgery for patients with lymph node metastasis are poor regardless of the sites of nodal metastasis.     

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes

BACKGROUND: The American Joint Committee on Cancer (AJCC) TNM classification for breast carcinoma had not been changed for 15 years, since the publication of the third edition in 1987. However, in the sixth edition, published in 2002, significant modifications were made with regard to the number of metastatic axillary lymph nodes. The authors investigated whether the sixth edition of the TNM classification provided more reliable prognostic information compared with the third edition. METHODS: The records of 1230 patients who underwent surgery for invasive breast carcinoma between 1993 and 1999 were reviewed. Each patient was assigned to axillary lymph node and disease stage groups according to the 1987 and 2002 AJCC TNM classifications. Disease-free survival (DFS) curves were calculated and plotted using the Kaplan-Meier method and the two-sided log-rank test was used to compare the survival curves of the patient groups. RESULTS: Of the 1067 patients who were classified as having Stages II and III disease according to the 1987 classification, 411 (38.5%) were shifted to higher disease stages using the 2002 classification. Among the 1987 Stage IIA, Stage IIB, and Stage IIIA patients, the DFS rates of the patients who were shifted to higher stages of disease were significantly worse than those of the patients for whom the stage of disease was not changed. Among those patients classified as having T4anyNM0 (Stage IIIB) disease according to the 1987 classification, there was no survival difference noted between those patients with T4N0,1,2M0 disease (who formed the Stage IIIB group) and those with T4N3M0 disease (who formed the Stage IIIC group) according to the new staging system. Of the 221 patients who formed the new Stage IIIC group, 12.2% were classified as having Stage IIA disease, 42.1% as having Stage IIB disease, 38.9% as having Stage IIIA disease, and 6.8% as having Stage IIIB disease according to the 1987 classification. The survival rates of these Stage IIA, Stage IIB, and Stage IIIA patients were not found to be significantly different; however, the survival of patients in the Stage IIIB group was found to be significantly worse than the survival of the patients in the other disease stage groupings, and the patients in the Stage IIIC group were not a prognostically homogeneous group. On the basis of these results, the authors placed patients with T4anyNM0 disease in the same group (Stage IIIB). When the 2002 classification was rearranged in this manner, patients with Stage IIIC disease formed a homogeneous group; the 5-year DFS rate of patients with Stage IIIB disease was found to be significantly worse than that for patients with Stage IIIC disease (P = 0.0011). CONCLUSIONS: In the 2002 TNM classification for breast carcinoma, patients with T4anyNM0 disease should form a distinct stage grouping and this stage grouping (Stage IIIC) should be placed before Stage IV, and Stage IIIB disease groupings should include patients with T1,2,3N3M0 disease. In this way, the authors hope that the 2002 AJCC TNM classification, which provides more reliable prognostic information than the 1987 classification, will become more refined.     

The role of sentinel lymph node biopsy for melanoma

Regional lymph nodes are a common site of melanoma metastases, and the presence or absence of melanoma in regional lymph nodes is the single most important prognostic factor for predicting survival. Furthermore, identification of metastatic melanoma in lymph nodes and excision of these nodes may enhance survival in a subgroup of patients whose melanoma has metastasized only to their regional lymph nodes and not to distant sites. Sentinel lymph node (SLN) biopsy was developed as a low morbidity technique to stage the lymphatic basin without the potential morbidity of lymphedema and nerve injury. The presence or absence of metastatic melanoma in the SLN accurately predicts the presence or absence of metastatic melanoma in that lymph node basin. When performed by experienced centers, the false-negative rate of SLN biopsy is very low. As such, the nodal basin that contains a negative SLN will usually be free of microscopic disease. Since occult micrometastatic disease affects only 12% to 15% of patients with melanoma, selective SLN dissection allows up to 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding the complications usually associated with that procedure. While standard pathologic evaluation of lymph nodes may miss metastatic melanoma cells, more sensitive techniques are developing which may identify micrometastases more accurately. The clinical significance of these micrometastases remains unknown and is the subject of active investigations.     

Local lymph node involvement does not predict poor outcome in pediatric renal cell carcinoma

BACKGROUND: Local lymph node involvement in adults with renal cell carcinoma (RCC) is associated with poor outcome. The prognostic significance of local lymph node involvement in children with RCC has not been studied systematically. METHODS: A retrospective review of patients treated at St Jude Children's Research Hospital (Memphis, TN) and an extensive review of the medical literature were undertaken to evaluate the prognostic significance of local lymph node involvement in pediatric RCC. RESULTS: Thirteen patients with the diagnosis of RCC were treated at St. Jude since the hospital's inception in 1962. Four patients presented with lymph node-positive, distant metastasis-negative (N + M0) disease, and all 4 remain disease free after resection without adjuvant therapy (follow-up duration, 2-9 years). A systematic review of the literature including 243 pediatric patients with RCC revealed stage-specific survival rates of 92.5%, 84.6%, 72.7%, and 12.7% for Stage I-IV disease, respectively. Of 58 children with N + M0 RCC for whom outcome data were available, 42 (72.4%) were alive without disease at last follow-up. Among patients whose therapy could be discerned, those who received no adjuvant therapy fared as well (15 of 16 alive) as those who received various adjuvant treatments (22 of 31 alive). CONCLUSIONS: Children with lymph node-positive RCC in the absence of distant metastatic disease had a relatively favorable long-term prognosis, with survival rate nearly triple those of adult historical controls. Until highly effective therapies for RCC are identified, these children should not be exposed to adjuvant treatment. Further investigation of the biologic differences between adult and pediatric RCC is warranted.     

Prognostic role of p‐mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer

Despite the great interest in mammalian target of rapamycin (mTOR) as a potential anticancer therapy target, the prognostic role of mTOR in gastric cancer has not been elucidated. In this study, we investigated mTOR expression in gastric cancer tissues and in metastatic lymph nodes and examined its association with clinical outcome. A total of 290 patients with pT2b gastric cancer were enrolled in this study. Patients were divided into 3 groups according to metastatic lymph node status: Group 1 contained 96 patients without lymph node metastasis, Group 2 contained 102 patients with a few (1–2) metastatic lymph nodes and Group 3 contained 92 patients with extensive (>16) lymph node metastasis. Phosphorylated mTOR expression was determined immunohistochemically using tissue microarrays. p‐mTOR expression was observed in 36.5% of the gastric cancer tissues in Group 1, 39.2% in Group 2 and 60.9% in Group 3. A significant correlation was found between p‐mTOR expression in gastric cancer tissues and in metastatic lymph nodes. The Borrmann type in Group 1, perineural invasion and p‐mTOR expression in metastatic lymph nodes in Group 2 and p‐mTOR expression in metastatic lymph nodes in Group 3 were found to be independent prognostic factors of disease‐free survival. The 5‐year disease free survival rate of Group 2 patients was 84.4% in negative p‐mTOR and 66.1% in positive p‐mTOR expression in metastatic lymph nodes (p = 0.015). The 5‐year disease free survival rate of Group 3 patients was 37.3% in negative p‐mTOR and 14.9% in positive p‐mTOR expression in metastatic lymph nodes (p = 0.037). There was a linear correlation between the rate of tumor recurrence and mTOR expression scores in metastatic lymph nodes. In pT2b gastric cancer, p‐mTOR expression in gastric cancer is associated with the extent of lymph node metastasis, and p‐mTOR expression in metastatic lymph nodes is correlated with poor disease‐free survival. mTOR may harbor significant potential for a prognostic biomarker and therapeutic target for gastric cancer treatment.     

Prognosis of level V malignant melanoma

Level V melanomas have been reported to have a poor prognosis, but in-depth analyses of prognostic factors and treatment have not been reported. From 1952 through 1982, 41 patients presented with primary Clark's Level V melanomas. There were 23 patients who presented with clinical Stage I disease and 18 with Stage II. Among Stage I patients, 9 were treated by wide excision alone and 13 underwent wide excision plus prophylactic regional lymph node dissection (RLND); 8 of 13 patients had histologically positive nodes. Twelve Stage II patients were treated by wide excision and RLND (including three hemipelvectomies), and four refused surgery. The 5-year survival was 52%. For Stage I patients, survival was 62% and disease-free survival (DFS) 28% at 5 years; 6 of 10 recurrences were local or regional only. Prophylactic RLND reduced the incidence of recurrence but did not appear to influence survival rates. Among 14 evaluable Stage II patients, overall survival was 60% and DFS 42% at 3 years; of 4 patients who subsequently had a recurrence, 3 had distant metastases. All seven patients with distant metastases at the time of first recurrence died of disease within 14 months (median, 4 months) of detection of metastatic disease. Primary melanomas of the foot (11 patients) and trunk (4 patients) appeared to have a worse prognosis than other sites. Ulceration (seen in 21 patients) did not appear to significantly influence outcome. These data suggest that most patients with Level V melanoma present with clinically localized disease. Prophylactic RLND did not significantly affect overall survival. The invasiveness of these deep tumors appears to reduce the influence of other factors, including primary site, sex, race, and ulceration. The prognosis of patients with Level V melanoma, even with clinically or histologically positive lymph nodes, is not hopeless, and these patients should be treated aggressively.     

220例完全切除Ⅱ期非小细胞肺癌术后患者的生存分析

Background and Objective:Surgery is the main therapy for patients with stage-Ⅱ non-small cell lung cancer(NSCLC),but patients still have an unsatisfactory prognosis even though complete resection is usually possible.Adjuvant chemotherapy provides low rates of clinical benefit as well.We retrospectively analyzed prognostic factors of patients with completely resected stage-Ⅱ NSCLC to find patients with unfavorable factors for proper management.Methods:Clinical data of 220 patients with complete resections of...     

Metastatic carcinoma of the neck from an unknown primary

From 1974 to 1984, 31 patients with metastatic carcinoma to the neck from an unknown primary were treated with radiation therapy. On review, three groups were identified based on presentation and treatment. Group I consists of 19 patients treated with curative intent. They all presented with cervical adenopathy, 11 patients with N1 disease, 2 with Stage N2A disease, 1 with Stage N2B disease, 4 with N3A disease, and 1 with unknown stage. The majority of patients were treated with portals encompassing the nasopharynx, oropharynx, hypopharynx, and neck to a dose of 5000 rad followed by boosts of 1000-1500 rad. The overall 2-year NED survival in this group was 63% (12/19). The most significant prognostic factor was the stage of the metastatic nodes. The NED survival rate for the 14 patients with Stage N1 and N2 was 86% (12/14). Histology of the lesions was not an important factor in the outcome. In Group II there are six patients who received palliative treatment because of large, fixed, cervical nodes. Three of these patients (50%) died within 2 months of completion of treatment. Group III consists of six patients who presented with supraclavicular adenopathy. All had persistent or recurrent disease within 19 months. We have concluded that in patients with metastatic carcinoma to the cervical nodes from an unknown primary, radiation therapy to the neck and suspected areas of primary disease may play an important role in cure, particularly in early stage disease.     

Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma

BACKGROUND: Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer. METHODS: Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed. RESULTS: The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years. CONCLUSION: The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.     

Prognostic variability among nonsmall cell lung cancer patients with pathologic N1 lymph node involvement. Epidemiological figures with strong clinical implications

BACKGROUND: Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement. METHODS: The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection. RESULTS: The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor. CONCLUSIONS: N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.     

The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced,high‐risk,lymph node‐metastatic melanoma

BACKGROUND:

The objective of this study was to evaluate the impact of adjuvant radiation therapy (RT) on regional recurrence and survival after therapeutic lymphadenectomy (TL) for clinically advanced, lymph node‐metastatic melanoma.

METHODS:

Six hundred fifteen patients who had clinically advanced, regional lymph node‐metastatic disease underwent TL. All patients were appropriate potential candidates for adjuvant RT (enlarged or multiple positive lymph nodes, extracapsular extension) because of a high risk for regional recurrence regardless of whether or not they received RT. Patient‐related, tumor‐related, and treatment‐related variables that were associated with recurrence, survival, and treatment‐related morbidity with and without RT were analyzed.

RESULTS:

The median follow‐up was 5 years. The actuarial 5‐year regional lymph node basin control rate was 81%. On multivariate analysis, the number of positive lymph nodes, the number of lymph nodes removed, and the use of adjuvant RT were associated with improved regional control. Treatment‐related morbidity, particularly lymphedema, was increased with the use of adjuvant RT and an inguinal site of lymph node metastases. At last follow‐up, 268 patients were alive with actuarial 5‐year distant metastasis‐free survival (DMFS) and disease‐specific survival (DSS) rates of 40% and 48%, respectively. On multivariate analysis, DMFS and DSS both were influenced by the number of positive lymph nodes and the number of lymph nodes removed. In addition, DSS was influenced by primary tumor thickness and the receipt of adjuvant RT.

CONCLUSIONS:

Adjuvant RT was associated with improved regional lymph node basin control compared with TL alone in patients with high‐risk, clinically advanced, lymph node‐metastatic melanoma. Although it is a regional therapy, adjuvant RT also may have an impact on DSS. Cancer 2009. © 2009 American Cancer Society.     

Improved survival of patients with stage II melanoma of the extremity using hyperthermic isolation perfusion with 1-phenylalanine mustard

Between 1964 and 1983, 65 patients with Stage II extremity melanoma were treated in a nonrandomized fashion with wide local excision, lymph node dissection, and hyperthermic perfusion with 1-phenylalanine mustard at 1.0-1.5 mg/kg. Southwest Oncology Group Stage II criteria were used, including IIA (node positive), IIB/C (recurrent local/regional), or both. During the study interval, literature reports of 5-year survival for Stage II melanoma ranged from 6% to 50% and averaged approximately 26% to 30%. In this study group, 40% of patients had recurrent disease confined to regional lymph nodes, 33% had recurrent cutaneous disease, and 26% had recurrent disease in both locations. Survival for all Stage II patients at 5 years was 56.6%, and 40% at 10 years. When recurrent disease was confined to regional nodes only (IIA), survival at 5 years was 70.5%, and 40% at 10 years. Survival for patients with Stage IIB/C disease at 5 and 10 years was 58% and 43.7%. When recurrent melanoma was present in both skin and nodes, 5-year survival was 29%. The present study indicates that aggressive treatment of Stage II extremity melanoma, which includes hyperthermic isolation perfusion, can prolong survival in these high-risk patients.     

Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study

BACKGROUND: Axillary lymph node status is a powerful prognostic factor in breast carcinoma; however, complications after axillary lymph node dissection are common. Sentinel lymph node biopsy is an alternative staging procedure. The sentinel lymph node postulate is that tumor cells migrating from the primary tumor colonize one or a few lymph nodes before colonizing subsequent lymph nodes. To validate this hypothesis, the distribution of occult and nonoccult metastases in sentinel and nonsentinel lymph nodes was evaluated. METHODS: Original pathology material was reviewed from 431 patients enrolled on a multicenter validation study of sentinel lymph node biopsy in breast carcinoma patients. Paraffin embedded tissue blocks of sentinel and nonsentinel lymph nodes were obtained for 214 lymph node negative patients. Additional sections from 100 and 200 microm deeper into the paraffin block were examined for the presence of occult metastatic carcinoma. Both routine and cytokeratin immunohistochemical stains were employed. RESULTS: Metastases were identified in 15.9% of sentinel lymph nodes and 4.2% of nonsentinel lymph nodes (odds ratio [OR] 4.3[ P < 0.001]; 95% confidence interval [95% CI], 3.5-5.4). Occult metastases were identified in 4. 09% of sentinel lymph nodes and 0.35% of nonsentinel lymph nodes (OR 12.3 [P < 0.001]; 95% CI, 5.6-28.6). The overall case conversion rate was 10.3%. All the occult metastases identified were < or = 1 mm in greatest individual dimension. The likelihood (OR) of metastases in nonsentinel lymph nodes was 13.4 times higher for sentinel lymph node positive than for sentinel lymph node negative patients (P < 0. 001; 95% CI, 6.7-28.1). CONCLUSIONS: The distribution of occult and nonoccult metastases in axillary lymph nodes validates the sentinel lymph node hypothesis. In addition, pathology review of cases confirmed the authors' previously reported finding that the sentinel lymph nodes are predictive of the final axillary lymph node status. Occult metastatic disease is more likely to be identified in sentinel lymph nodes, allowing future studies to focus attention on one or a few sentinel lymph nodes. However, the relation between occult metastatic disease in sentinel lymph nodes, disease free survival, and overall survival must be evaluated prior to endorsing the intensive analysis of sentinel lymph nodes in routine practice. [See editorial on pages 971-7, this issue.] Copyright 2000 American Cancer Society.     

Survival analysis after resection of metastatic disease followed by peptide vaccines in patients with Stage IV melanoma

BACKGROUND: Metastatic melanoma carries a poor prognosis, with a median survival of 7-9 months. Surgical resection of metastatic disease has been advocated to improve survival. Immunotherapy after metastasectomy may further improve the outcome for high-risk resected disease. METHODS: Charts from patients treated on institutional vaccine trials were analyzed. Patients with American Joint Committee on Cancer (AJCC) Stage IV melanoma who underwent surgical resection of metastatic sites followed by treatment on a peptide vaccine trial were eligible for this study. Survival was calculated from the date of enrollment on the clinical trial. RESULTS: Forty-one patients met inclusion criteria. The median age was 56.5 years, with approximately equal numbers of men and women. The ECOG performance status was 0 in all patients. Approximately 46% of patients underwent resection of visceral metastases before vaccine. The median follow-up was 5.6 years. The median overall survival was 3.8 years. CONCLUSIONS: In selected patients with AJCC Stage IV melanoma, resection of metastatic disease followed by vaccine therapy can result in long-term survival.