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D L Morton

Publications and source records attributed to D L Morton.

At least 73 records · Page 4Linked to original sources
PubMed1999

Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group.

OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Adolescent↗
PubMed1999

Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complications.

OBJECTIVE: Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS: We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS: The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION: Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

Adult↗
PubMed1999

Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients.

PURPOSE: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse. PATIENTS AND METHODS: Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival. RESULTS: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNA markers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P =.03), were 60 years of age or younger (P <.05), and/or were MM-positive (P <.001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P =.02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P =. 01). CONCLUSION: H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.

Adult↗
PubMed1999

Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma.

PURPOSE: Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. PATIENTS AND METHODS: Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. RESULTS: The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. CONCLUSION: The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.

Adult↗
PubMed1999

Vaccine therapy for patients with melanoma.

Investigation into the therapeutic use of vaccines in patients with metastatic melanoma is critically important because of the lack of effective conventional modalities. The most extensively studied melanoma vaccines in clinical trials are whole-cell preparations or cell lysates that contain multiple antigens capable of stimulating an immune response. Unfortunately, in the majority of studies, immune responses to these vaccines have not translated into a survival advantage. Advances in tumor cell immunology have led to the identification of candidate tumor cell antigens that can stimulate an immune response; this, in turn, has allowed for refinements in vaccine design. However, the exact tumor antigens that should be targeted with a specific vaccine are unknown. The univalent antigen vaccines, which have greater purity, ease of manufacturing, and reproducibility compared with polyvalent vaccines, may suffer from poorer efficacy due to immunoselection and appearance of antigen-negative clones within the tumor. Novel approaches to vaccine design using gene transfection with cytokines and dendritic cells are all promising. However, the induction of immune responses does not necessarily confer a therapeutic benefit. Therefore, these elegant newer strategies need to be studied in carefully designed clinical trials so that outcomes can be compared objectively with standard therapy. If survival is improved with these vaccine approaches, their ease of administration and lack of toxicity will firmly entrench active specific vaccine immunotherapy as a standard modality in the treatment of the melanoma patient.

Cancer Vaccines↗
PubMed1998

Tumor-associated antigen TA-90 immune complex assay predicts subclinical metastasis and survival for patients with early stage melanoma.

BACKGROUND: TA-90 is a tumor-associated antigen first identified in the urine and sera of patients with metastatic melanoma. In the early stages of disease, TA-90 is present in circulating immune complexes (ICs) that may be detected with an antigen specific enzyme-linked immunosorbent assay (ELISA). In this study, the authors evaluated the efficacy of the TA-90 IC assay in detecting subclinical metastasis of early stage melanoma and predicting the survival of patients with this disease. METHODS: Archival sera were collected preoperatively from 114 patients who underwent wide excision with or without regional lymphadenectomy in the treatment of clinical Stage I melanoma. Sera were analyzed for TA-90 IC in a blinded fashion, and results were correlated with the patient's clinical course as determined by database and chart review. Subclinical metastases were considered present at the time of surgery if the lymphadenectomy specimen was pathologically positive and/or the patient subsequently developed recurrence. RESULTS: The TA-90 IC assay predicted subclinical metastasis in 43 of 56 patients (P < 0.0001), with 14 false-positive and 13 false-negative results. Sensitivity and specificity for the detection of occult metastasis were 77% and 76%, respectively. Positive and negative predictive values were 75% and 77%, respectively. Fifteen of 18 tumor positive regional lymph node basins (83%) and 34 of 46 recurrences (74%) were accurately predicted when considered independently (P < 0.004). Preoperative TA-90 IC status was also highly correlated with survival: 5-year overall and disease free survival rates were 63% and 46%, respectively, for the TA-90 IC positive group, compared with 88% and 82%, respectively, for the TA-90 IC negative group (P=0.0001). A multivariate analysis with standard prognostic variables identified preoperative TA-90 IC status as a strong, independent prognostic factor for both overall and disease free survival. CONCLUSIONS: To the authors' knowledge, TA-90 is the first tumor marker that accurately predicts subclinical metastatic disease and survival for patients with early stage melanoma. For this reason, the TA-90 IC assay has the potential to improve dramatically the prognostic evaluation of patients with this disease. Its role in postoperative risk stratification and early detection of recurrence is being evaluated in a prospective study.

Adult↗
PubMed1998

Ratio of IgG:IgM antibodies to sialyl Lewis(x) and GM3 correlates with tumor growth after immunization with melanoma-cell vaccine with different adjuvants in mice.

Human melanoma cells (from biopsies and culture) express sialyl-Lewis(x) and sialyl Lewis(a), the ligands for ECAM. These ligands may facilitate tumor progression and metastasis in human cancers. To test whether the antibodies to these ligands inhibit tumor progression, IgG and IgM responses to sLe(x) and sLe(a) were induced in C57BL/6j mice (n = 76) by immunization with human melanoma cells, with or without adjuvants (BCG, MPL, KLH). Control mice were treated with saline or BCG. Tumor growth and antigen expression were monitored after challenge with B16 mouse melanoma cells expressing sLe(x), sLe(a) and the ganglioside GM3. Tumor growth was reduced in mice immunized with BCG alone or cells with BCG or MPL, while tumors in mice receiving cells without adjuvants grew larger than in the control. Augmentation of IgM titers to sLe(x) and GM3 after immunization with BCG, or with cells with BCG or MPL correlated with retarded tumor growth, while increased IgG titers to sLe(x) significantly correlated with aggressive tumor growth in mice immunized with cells without adjuvants. SLe(x), sLe(a) and GM3 were expressed in tumors from mice treated with saline or BCG. SLe(x) expression, in particular, was lost in tumors growing in mice immunized with cells with or without adjuvants. Anti-sLe(x) antibodies may promote or prevent tumor growth by antigenic modulation or by cytotoxic killing of tumor cells. Since early anti-sLe(x) IgM correlated with tumor regression, in contrast to anti-sLe(x) IgG, it may serve as a potential early endpoint for the effectiveness of melanoma vaccines expressing the antigens.

Animals↗
PubMed1998

Tumor doubling time: a selection factor for pulmonary resection of metastatic melanoma.

BACKGROUND AND OBJECTIVES: Melanoma patients have a 20-27% rate of 5-year survival after surgical resection of pulmonary metastases. We evaluated tumor doubling time (TDT) and other prognostic factors in an attempt to identify candidates for pulmonary metastasectomy. METHODS: Review of our large melanoma database identified 129 patients who underwent complete or partial resection of pulmonary metastases. At least two preoperative chest roentgenograms were available for 45 patients; these images were used by a single examiner to measure tumor width and length. The mean of the diameters was plotted against time on semilogarithmic paper: the slope of the line approximated tumor growth rate, and TDT was proportional to the inverse of the tumor growth rate. RESULTS: For the 45 patients with a calculated TDT, median survival was 23.1 months and 5-year survival rate was 15.6% (7/45). By multivariate analysis, the only prognostically significant factors were TDT (P=0.006) and type of pulmonary resection (P=0.022). When TDT was <60 days, median survival was 16.0 months, and 5-year survival rate was zero; when TDT was > or = 60 days, median survival was 29.2 months (log-rank test; significant at P < 0.0001) and 5-year survival rate was 20.7% (6/29) (P < 0.0001). CONCLUSIONS: TDT is the most significant preoperative prognostic factor for patients undergoing pulmonary resection of metastatic melanoma. If TDT is <60 days, a preoperative neoadjuvant regimen of chemotherapy and biologic therapy is recommended. Pulmonary metastasectomy should not be attempted if TDT cannot be increased to > or = 60 days by systemic therapy.

Adolescent↗
PubMed1998

Lymphatic mapping and sentinel lymphadenectomy for melanoma.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) for patients with clinical Stage I melanoma was developed to determine the tumor status of the regional lymphatic basin without elective regional node dissection. Only individuals with histologically confirmed sentinel node (SN) metastases undergo complete regional node dissection, sparing those with tumor-free SN the morbidity of this procedure. Studies worldwide have confirmed the validity of the SN concept and the accuracy of SLND as a staging procedure. The incidence of false-negative SN and the rate of recurrence in the regional node basin have been low. Routine preoperative lymphoscintigraphy and refinements in surgical technique have improved the accuracy of SLND for melanoma, making it the nodal staging procedure of choice when undertaken by an experienced nuclear medicine physician, surgical oncologist and pathologist. Ongoing studies are investigating the impact of SLND on survival as well as the prognostic significance of micrometastasis detected by histopathologic and molecular techniques.

Humans↗
PubMed1998

Overview of melanoma vaccines: active specific immunotherapy for melanoma patients.

Although a phase III trial has yet to show a statistically significant improvement in the disease-free or overall survival of melanoma patients receiving vaccine therapy, several phase II trials have shown enhanced disease-free and overall survival of patients who develop a humoral and/or cellular response to a melanoma vaccine. The challenge of active specific immunotherapy research is to determine which combination of humoral and cellular immune responses optimizes clinical outcome and how to monitor the immune response effectively. This review identifies key components of a successful melanoma vaccine, discusses new ways to modulate and stimulate the immune system, and summarizes some of the important clinical trials of active specific immunotherapy for patients with melanoma.

Cancer Vaccines↗
PubMed1998

Positron emission tomography plus serum TA90 immune complex assay for detection of occult metastatic melanoma.

BACKGROUND: Whole-body positron emission tomography (PET) using 18F-fluorodeoxyglucose is very sensitive for detection of metastatic melanoma. We previously reported the accuracy of a serum TA90 enzyme-linked immunosorbent assay (ELISA) in predicting the recurrence of early-stage melanoma. This serum ELISA measures a circulating immune complex composed of TA90 a tumor-associated 90-kD glycoprotein antigen, and its IgG antibody. We hypothesized that using PET examination in conjunction with our serum TA90 ELISA would increase the detection of occult melanoma lesions. STUDY DESIGN: From November 1, 1993 to December 31, 1995, 87 patients underwent PET examination followed within 6 weeks by serum TA90 ELISA. All patients had undergone complete resection of local, regional, or distant metastatic melanoma and had no clinical evidence of disease at the time of PET examination. Each patient had complete followup for 12 months after PET examination. The clinical course was determined by chart review of clinical and radiographic findings. RESULTS: Of the 25 patients who experienced recurrence of disease within 6 months of followup, 22 (88%) had a positive result on one or both tests. Of the 52 patients with a negative result on both tests, 49 (94%) remained disease-free at 6 months of followup. Of the 14 patients who developed distant metastases within 6 months after PET examination, 13 (93%) had a positive PET examination and/or a positive TA90 ELISA. CONCLUSIONS: The TA90 ELISA correlated well with PET examination for detection of metastatic melanoma. The high sensitivity of PET examination plus TA90 ELISA suggests that this combination may have a role in the surveillance of patients at high risk of developing metastatic melanoma.

Adolescent↗
PubMed1998

Augmentation of IgM antibody to gp43 tumor-associated antigen peptide by melanoma cell vaccine.

We previously reported that gp43 tumor-associated antigen peptide (DLTMKYQIF; designated 810 antigen) on human melanoma cells is recognized by IgM human monoclonal antibody L92 and by cytotoxic T lymphocytes (CTL). In this study, we retrospectively tested sera of 44 patients with regional metastatic melanoma (22 who recurred within 1 year and 22 who survived longer than 5 years) to determine if antibody responses to 810 antigen could be induced by immunization with an allogeneic melanoma cell vaccine that contained 810 peptide. IgM and IgG antibodies were assessed by enzyme-linked immunosorbent assay using a synthetic 810 nonamer peptide. A significant augmentation of IgM antibody was demonstrated 4 weeks after initiation of vaccine therapy, and the IgM level was significantly higher in patients who survived more than 5 years. The antigen epitope recognized by antibodies was located within TMKYQI. Of this epitope sequence, K appears to play a central role in antigenicity. The 810 antigen recognized by antibody and CTL may have clinical relevance as a potential source of melanoma vaccine.

Antibodies, Neoplasm↗
PubMed1998

Antibody responses to melanoma/melanocyte autoantigens in melanoma patients.

Melanogenesis-related proteins play important roles in melanin synthesis and antigenicity of melanomas. Identification of highly expressed melanoma-associated antigens (MAA) that are immunogenic in humans will provide potential targets for cancer vaccines. Melanogenesis-related proteins have been shown to be MAA. Autoantibody responses to these MAA have been shown to react with melanoma cells and melanocytes, and suggested to play a role in controlling melanoma progression. To assess antibody responses to potential melanoma/melanocyte autoantigens, the open-reading frame sequences of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and melanoma-associated glycoprotein antigen family (gp100/pmel17) genes were cloned and expressed as recombinant proteins in E. coli. Purified recombinant antigens were employed to detect antibodies in sera of melanoma patients and normal healthy donors. By affinity enzyme-linked immunosorbent assay and western blotting, all recombinant antigens were shown to be antigenic. The main subclass of antibody response to these antigens was IgG. Most importantly this study demonstrated anti-TRP-2 and anti-gp100/pmel17 IgG responses in melanoma patients. Only one of 23 normal donors had an antibody response to the antigens tested. MAA-specific IgG antibodies in sera were assessed in melanoma patients (n = 23) pre- and post-polyvalent melanoma cell vaccine treatment. Polyvalent melanoma cell vaccine treatment enhanced anti-MAA antibody responses; however, only anti-TRP-2 and anti-gp100/pmel17 antibody response was enhanced. These studies suggest that four melanogenesis-related proteins are autoimmunogenic and can be used as potential targets for active-specific immunotherapy.

Antibody Formation↗
PubMed1998

Anti-tyrosinase-related protein-2 immune response in vitiligo patients and melanoma patients receiving active-specific immunotherapy.

Several melanosome glycoproteins have been shown to be antigenic in humans. Correlation of antigen-specific immune responses in patients with the autoimmune disease vitiligo, therapy-induced hypopigmentation, and cutaneous melanoma has not been well studied. We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes. TRP-2 recombinant protein was synthesized for western blot and affinity anti-TRP-2 enzyme-linked immunosorbent assay. We demonstrated that patients with malignant melanoma, vitiligo, and active-specific immunotherapy-induced depigmentation had significant anti-TRP-2 IgG titers. The highest level of anti-TRP-2 IgG response was found in vitiligo patients. Induction and enhancement of anti-TRP-2 IgG responses were observed in melanoma patients treated with a polyvalent melanoma cell vaccine containing TRP-2. Active-specific immunotherapy could induce and/or augment the TRP-2 IgG antibody titers. Melanoma patients who developed hypopigmentation and had improved survival after polyvalent melanoma cell vaccine had significantly augmented anti-TRP-2 antibody responses compared with patients with poor prognosis. This study demonstrates that TRP-2 autoantigen is immunogenic in humans. TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo patients and melanoma patients responding to immunotherapy who have induced hypopigmentation.

Antibodies↗
PubMed1998

Is the survival of melanoma patients receiving polyvalent melanoma cell vaccine linked to the human leukocyte antigen phenotype of patients?

PURPOSE: An allogeneic polyvalent melanoma cell vaccine (PMCV) has been shown to be efficacious in improving overall survival of patients with malignant melanoma in a phase II clinical setting. The PMCV consists of three allogeneic melanoma cell lines. The objectives of the study were to determine (1) whether the survival of melanoma patients who received PMCV was related to the patient's human leukocyte antigen (HLA) class I phenotype matching the HLA class I phenotype of the PMCV, and (2) whether PMCV clinical efficacy was correlated to melanoma patients with a particular HLA phenotype(s). MATERIALS AND METHODS: PMCV was given to 69 melanoma patients with American Joint Committee on Cancer (AJCC) stage I to IV disease status. The PMCV and patients lymphocytes were typed for HLA-A and -B. A correlation was made between the HLA expression of PMCV lines and the HLA of patients to their survival status. A second correlation was made between the HLA of patients and survival independent of the PMCV HLA phenotype. RESULTS: Patients whose HLA phenotype (A3/11 and B7/44) matched the PMCV lines had a better overall survival (P < .029). Analysis of HLA expression of patients independent of PMCV HLA to survival showed that HLA-A25 phenotype patients had a significantly better overall survival (P = .006). HLA-B35 patients had a poorer survival outcome (P = .019). CONCLUSION: The studies indicate that overall survival following PMCV treatment in melanoma patients significantly correlates with their HLA phenotypes. These correlations may be related to the host immune response to the PMCV or due to differences in the clinical course of melanoma in patients with different HLA types.

Adult↗
PubMed1998

Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.

PURPOSE: The mechanisms that underlie the clinical efficacy of melanoma vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Cancer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine (PMCV), might be correlated with its effect on overall survival (OS). PATIENTS AND METHODS: Seventy-seven patients began PMCV therapy after complete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guerin (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-associated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune competence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. RESULTS: Median follow-up time was 31.5 months. Within the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P=.0001) and IgG titers (P=.0001), and in the DTH response to PMCV (P=.0001). Univariate analysis showed that high anti-TA90 IgM titer and strong PMCV-DTH were associated with improved survival (P=.051 and .0173, respectively), whereas elevated anti-TA90 IgG was correlated with decreased survival (P=.0119). Multivariate analysis considering clinical variables and PMCV immune responses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as significant independent variables influencing survival following PMCV immunotherapy (P=.0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefore were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival rate were more than 76 months and 75%, respectively, if both anti-TA90 IgM and PMCV-DTH responses were strong (> or = 800 and > or = 7 mm, respectively; n=29); 32 months and 36%, respectively, if only one response was strong (n=35); and 19 months and 8%, respectively, if neither was strong (n=13) (P < .0001). CONCLUSION: PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.

Adult↗
PubMed1998

Surgical resection as the treatment of choice for melanoma metastatic to the lung.

Available data suggest that patients who have a limited number of pulmonary metastases may benefit from complete surgical resection if they have favorable prognostic features such as a long TDT and a long DFI. If a patient is not a surgical candidate because of radiographic evidence of extrapulmonary disease, a short TDT, or a short DFI, then concurrent or sequential biochemotherapy offers the best chance for a complete response and remission.

Antineoplastic Combined Chemotherapy Protocols↗