Retrospective Observational Study to Determine the Epidemiology and Treatment Patterns of Patients with Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) poses a serious therapeutic challenge due to the occurrence of frequently aggressive, heterogenic, and metastatic tumours. The absence of therapeutic targets for traditional therapies is a hindrance to establishing a standardised therapy for TNBC. There is limited TNBCs epidemiological and real-world data about TNBC treatment regimens in Poland. We retrospectively analysed clinical data from our hospital registry from 2015 and 2020. A total of 8103 individuals with breast cancer were admitted to the MSCI, while 856 (10.6%) were diagnosed with TNBC. Most of the early-stage or locally advanced TNBC individuals had underlying conditions, presented mostly poorly differentiated (G3) stage II tumours and featured a bi-modal age distribution. On average, one-third of all tested TNBCs carried BRCA mutations and its identification impacted surgery preference. We observed a significant increase in the use of systemic therapy among TNBCs, whereas carboplatin and dose-dense regimens showed the most prominent upsurge in the neoadjuvant setting. Moreover, the use of neoadjuvants was positively correlated with less invasive breast and lymph node surgeries. The presented data align with general trends observed in other countries and will contribute to expanding knowledge in the planning of treatment regimens and their outcomes.

Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2-Positive Breast Cancer: Real-World Data from the National Institute of Oncology in Poland.

Neoadjuvant systemic therapy has now become the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve the rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular, in patients with more aggressive breast cancer subtypes such as TNBC or HER2-positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and present the adverse effects of the applied therapies, opening discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

The long-term results and prognostic significance of cutaneous melanoma surgery using sentinel node biopsy with triple technique.

BACKGROUND: The sentinel lymph node biopsy (SLN) is a basic staging method in all primary cutaneous melanomas ≥pT1b. The standard technique is a triple technique consisting of preoperative lymphoscintigraphy, intraoperative blue-dye lymphography, and gamma-probe assessment. We performed the analysis of long-term results in a very large one-institution series of cutaneous melanoma patients. METHODS: We have analyzed treatment results of a group of 1764 consecutive patients with cutaneous melanoma, who underwent SLN biopsy between 1997 and 2008 in one tertiary center. Additionally, we have analyzed the outcomes of a group of 473 patients with positive SLN biopsy undergoing completion lymph node dissection (CLND). Median follow-up time was 5.3 years. RESULTS: Metastases to SLN (SLN+) were found in 19.9%. Eight-year overall survival (OS) rate in the entire group was 73.5%, 80% without SLN metastases (SLN-) and 50% in group with SLN+ (p < 0.001). Independent prognostic factors for OS were as follows: presence of metastases to SLN, primary tumor ulceration, and higher mitotic index (>5/mm(2)) of primary tumor. The nodal recurrences in the biopsied lymphatic basin were 5.4%. The metastases to non-sentinel lymph nodes (NSLN found in 27% of patients with SLN+) correlated (on multivariable logistic regression analysis) with primary tumor thickness >4 mm, SLN metastatic deposit size >1 mm, and extracapsular involvement of SLN. In an additionally analyzed SLN+ group, the NSLN involvement was related to poorer prognosis (8-year OS rate NSLN- vs NSLN+: 59.6 vs. 34.7%, respectively). The independent prognostic factors for OS in the SLN+ group were a higher Breslow thickness and ulceration of primary tumor, metastases to more than 1 lymph nodes. CONCLUSIONS: The long-term results confirm crucial prognostic significance of SLN biopsy in cutaneous melanoma. We identified factors related to NSLN involvement, which in the future may limit indications for CLND.

The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study.

BACKGROUND: Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. METHODS: We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. RESULTS: One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0.015, respectively). CONCLUSIONS: We confirmed that many advanced GIST patients benefit from SU therapy with OS > 1.5 year. Primary tumor KIT/PDGFRA genotype and SU-induced AH, as surrogate of its antiangiogenic activity are two independent factors influencing both PFS and OS.

Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients.

Dendritic cells may be successfully used to induce in vivo-specific anti-tumor responses when combined with the appropriate antigen in the appropriate context. The purpose of this study was to evaluate efficacy of peptide-loaded DC vaccine in high-risk stage III melanoma patients after lymph node dissection (LND). HLA-A2+, -A1+, or -A3+ melanoma patients (N=22), stage III, N1b-N3, received 5­16 (median: 11) DC vaccines loaded with MHC class-I-restricted melanoma peptides respective to the patient's haplotype, and with autologous tumor lysate, if available. Vaccinated patients were matched to unvaccinated stage III controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, LND type, Breslow stage, and ulceration. Vaccination elicited cutaneous delayed-type hypersensitivity (DTH) or/and IFN-γ-producing CD8+ cell response to melanoma peptides in 15 of 22 patients. Three-year overall survival (OS) rate was 68.2% in the vaccinated group versus 25.7% in the control group, P value accounting for matching: 0.0290. In a Cox regression model, hazard ratio (HR) for death of vaccinated patients was 0.31 [95% confidence interval (CI): 0.10­0.94]. The corresponding values for 3-year disease-free survival rate were 40.9 versus 14.5%, P=0.1083; HR of recurrence for vaccinated, 0.46 (95% CI: 0.18­1.22). There was no grade>1 toxicity. The DC/peptide vaccine was well tolerated and elicited immune responses to melanoma antigens. Vaccinated patients had significantly longer OS after LND than the matched controls, but a significant improvement in the primary endpoint DFS was not achieved.

Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria.

PURPOSE: Prognosis in patients with sentinel node (SN)-positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy. PATIENTS AND METHODS: Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography. RESULTS: Patients with submicrometastases (< 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%. CONCLUSION: Patients with metastases < 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.

Risk of permanent stoma after resection of rectal cancer depending on the distance between the tumour lower edge and anal verge.

The distance between the anal verge and lower edge of rectal cancer is one of the most important factors affecting the feasibility of sphincter-preserving resection.The aim of the study was to assess the risk of permanent stoma after resection of rectal tumour depending on the distance between the tumour and the anal verge.Material and methods. The retrospective analysis covered 884 patients after resection of rectal cancer. The distance between the anal verge and the lowest edge of the tumour was measured during endoscopic examination. Surgical technique was similar in all cases. For statistical analysis, the chi-square test and Fisher exact test were used.Results. The overall rate of sphincter-preserving procedures was 71.8%, 90.1% of which were anterior resections. The greatest differences between the rate of anterior resections were noted for the segment between the 4th and the 5th centimetres: 30.1% for 4 cm vs 66.7% for 5 cm, p = 0.005. Overall, in 328 patients (37.1%) surgical treatment resulted in a permanent stoma. The number included: 246 (75.0%) patients after abdominosacral resection, 44 (13.4%) patients after the Hartmann procedure, three (0.9%) patients after proctocolectomy, and 28 (8.5%) patients after anterior resection, with a permanent stoma as a result of anastomotic leak. The overall rate of anastomotic leak was 11.7%. Formation of a defunctioning stoma in patients with a low-lying (6 cm from the anal verge) tumour reduced the risk of symptomatic anastomotic leak: 6.3% vs 20.5%; p = 0.049.Conclusions. Anterior resection of tumours located 6 cm from the anal verge is feasible in 90%. Anastomotic leak that requires reoperation increases the risk of permanent colostomy. In selected cases, formation of a defunctioning stoma after resection of low-lying rectal cancer can reduce the risk of permanent colostomy.

Cutaneous melanoma with nodal metastases in elderly people.

BACKGROUND: The impact of age on melanoma patient outcomes is uncertain. OBJECTIVE: The aim of the study was to analyze the characteristics and treatment outcomes in cutaneous melanoma patients ≥ 65 years of age with lymph node metastases. METHODS: We analyzed data from 849 consecutive patients with stage III cutaneous melanoma who were treated between 1994 and 2007 at one institution. Of these, 225 (26.5%) were ≥ 65 years of age. The characteristics and disease-specific survival (DSS) from lymph node dissection (LND) date of patients ≥ 65 years of age were compared with those of younger patients. Median follow-up time was 49 months (range: 6-140 months). RESULTS: In the ≥ 65 years group (51.6% men), the median Breslow thickness was 5.0 mm and 70% was ulcerated. The 5-year DSS rate was significantly lower in older patients (34%). Multivariate analysis identified older age as an independent prognostic factor for DSS in the overall group. Independent negative prognostic factors of DSS in the group of older stage III patients were identified as features of nodal metastases (extracapsular invasion, HR = 1.74, P = 0.009; and ≥ 4 involved lymph nodes, HR = 1.5; P = 0.008) and male sex (HR = 1.5; P = 0.039). CONCLUSIONS: This analysis showed that melanoma patients ≥ 65 years of age are characterized by a higher primary tumor stage and worse prognosis in the presence of regional node metastases than younger patients. Additionally, the results indicate that the same radical surgical therapy is necessary for patients ≥ 65 years old as in younger patients.

Multimarker reverse transcriptase-polymerase chain reaction assay in lymphatic drainage and sentinel node tumor burden.

PURPOSE: We assessed molecular (presence of melanoma cells markers in lymph fluid [LY]) and pathological features (sentinel lymph node [SN] tumor burden according to Rotterdam criteria, metastases microanatomic location) and correlated them with survival and melanoma prognostic factors in a group of patients with positive SN biopsy. METHODS: We analyzed 368 consecutive SN-positive patients after completion lymph node dissection (CLND). In 321 patients we obtained data on SLN microanatomic location/tumor burden (only 7 cases had metastases <0.1 mm); in 137 we additionally analyzed 24-hour collected LY after CLND (multimarker reverse transcriptase-polymerase chain reaction [MM-RT-PCR] with primers for tyrosinase, MART1 (MelanA), and uMAGE mRNA (27.7% positive samples)]. Median follow-up time was 41 months. RESULTS: According to univariate analysis, the following factors had a negative impact on overall survival (OS): higher Breslow thickness (P = .0001), ulceration (P < .0001), higher Clark level (P = .008), male gender (P = .0001), metastatic lymph nodes >1 (P < .0001), nodal metastases extracapsular extension (P < .0001), metastases to additional non-SNs (P = .0004), micrometastases size ≥ 0.1 mm (P = .0006), and positive LY MM-RT-PCR (P = .0007). SN tumor burden showed linear correlation with increasing Breslow thickness (P = .01). The 5-year OS rates for SLN tumor burden <0.1 mm, 1-1.0 mm, and >1.0 mm were 84%/66%/44%, respectively, and for positive and negative LY MM-RT-PCR 47%/0%, respectively. The independent factors for shorter OS (multivariate analysis): male gender, primary tumor ulceration, number of involved nodes ≥ 4, micrometastases size >1.0 mm, and, in additional model including molecular analysis-positive MM-RT-PCR results (hazard ratio [HR] 3.2), micrometastases size >1.0 mm (HR 1.13), and primary tumor ulceration (HR 2.17). Similar results were demonstrated for disease-free survival (DFS) data. CONCLUSIONS: SN tumor burden categories according to Rotterdam criteria and the positive result of LY MM-RT-PCR assay demonstrated additional, independent prognostic value in SN-positive melanoma patients, showing significant correlation with shorter DFS and OS.

Melanoma without a detectable primary site with metastases to lymph nodes.

OBJECTIVE: To compare outcomes of patients with clinical nodal melanoma metastases that occurred without a detectable primary tumor (melanoma of unknown primary site; MUP) with those with a known primary site (KPM). METHODS: We included data from 459 consecutive patients treated from 1994 to 2007 with radical therapeutic lymph node dissection (LND; stage IIIB, C) due to clinically palpable and pathologically confirmed lymph node metastases (229 axillary; 230 ilioinguinal). The median follow-up was 49 months. RESULTS: LND was performed in 59 cases (12.9%; 29 men, 30 women) due to MUP nodal metastases, including 33 axillary (14.4%) and 26 ilioinguinal (11.3%). In the MUP group, the 3- and 5-year survival rates were 48% and 41%, respectively. Similar rates were observed in patients with KPM, even with matched-pair analyses. Established prognostic factors (number of metastatic nodes, p=.005; extracapsular extension of metastases, p=.002) influenced survival in the MUP group. Relapses occurred in 31 (53%) and 299 (74.7%) cases in the MUP and KPM groups, respectively. CONCLUSIONS: Survival rates in the MUP and KPM groups were similar, and the same prognostic factors affected both. Thus, all MUP cases should be treated as standard stage III melanomas.

Surgery of primary melanomas.

Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy-excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure-is performed under local anesthesia as an elliptical incision with visual clear margins of 1-3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1-2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

Surgery combined with brachytherapy in patients with retroperitoneal sarcomas.

PURPOSE: The primary aim of this work was to analyze feasibility of combined treatment of retroperitoneal sarcomas (RS): surgery (S) and intraoperative brachytherapy (IOBRT). The secondary aim was to analyze results and complications after this treatment. MATERIAL AND METHODS: 84 patients with retroperitoneal sarcomas were qualified for combined treatment (S and IOBRT) between June 1998 and September 2006. 65 of the patients (77.4%) had local recurrences. Sarcomas with intermediate and high grade of histological malignancy (G2, G3 - 76.2%) were the most frequent within the all surgically treated patients. Resection ability (R0/R1) in analyzed group of patients was estimated as 85% (74 cases). After intraoperative evaluation, 57 (67.8%) patients were qualified for IOBRT. Since 2000, in 34 patients (60%) an adjuvant postoperative external beam radiation therapy (EBRT) in dose of 50 Gy was applied. Median follow-up of the surviving patients was 40 months. RESULTS: On the basis of the univariate analysis, relevant aspects negatively influencing overall survival rate within the RS group treated with IOBRT were as follows: surgery of sarcoma recurrence (p = 0.002), higher grade of histological malignancy (p = 0.05), histological type different than liposarcoma (p = 0.05) as well as no adjuvant EBRT (p = 0.05). On the basis of multivariate analysis one can ascertain that relevant factors negatively influencing LRFS in RS patients treated with IOBRT were: surgery due to recurrence of sarcoma (p = 0.008) and lack of EBRT (p = 0.01). CONCLUSIONS: Combined treatment (surgery and brachytherapy) was possible to be carried out on 68% of RS patients. The overall number of complications was quite high, however acceptable, taking into consideration the application of extensive, multi-organ treatments in case of sarcoma recurrences in this localization. The results suggest that the method of treatment will improve the final outcome when most of patients will be qualified for treatment of primary sarcomas in experienced centre.

Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations. METHODS: Total RNA was isolated from 29 frozen gastric GISTs and processed for hybridization on GENECHIP HG-U133 Plus 2.0 microarrays (Affymetrix). KIT and PDGFRA were analyzed by sequencing, while related mRNA levels were analyzed by quantitative RT-PCR. RESULTS: Fifteen and eleven tumours possessed mutations in KIT and PDGFRA, respectively; no mutation was found in three tumours. Gene expression analysis identified no discriminative profiles associated with clinical or pathological parameters, even though expression of hundreds of genes differentiated tumour receptor mutation and expression status. Functional features of genes differentially expressed between the two groups of GISTs suggested alterations in angiogenesis and G-protein-related and calcium signalling. CONCLUSION: Our study has identified novel molecular elements likely to be involved in receptor-dependent GIST development and allowed confirmation of previously published results. These elements may be potential therapeutic targets and novel markers of KIT mutation status.

Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes.

SUMMARY BACKGROUND DATA: The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which represents different biology. METHODS: The slides of positive SN from 3 major centers within the European Organization of Research and Treatment of Cancer (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the completion lymph node dissection (CLND) and disease outcome as disease-free survival (DFS) and overall survival (OS) was calculated. RESULTS: In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm. Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm, 61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity. CONCLUSION: This large multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm have the same prognosis as SN negative patients and can be spared a CLND. A <0.2 mm cut-off for SUB-micrometastases does not seem correct for melanoma, as 10% additional nodal positivity is found.

Molecular staging by multimarker reverse transcriptase-polymerase chain reaction assay of lymphatic drainage and blood from melanoma patients after lymph node dissection.

Reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated detection of melanoma cells may be a prognostic factor for disease outcome. We investigated the presence of melanoma cells in lymphatic drainage and blood in melanoma patients after lymph node dissection (LND) via the highly sensitive multimarker (MM) RT-PCR assay. We collected 24-h lymph fluid (LY) and peripheral blood (BL) from 107 stage III melanoma patients after radical LND (59 axillary and 48 ilioinguinal LND). Tyrosinase, MART1 and uMAGE mRNA levels were determined by RT-PCR to detect melanoma cells, and the presence of at least one marker signified a positive result. All patients underwent follow-up (median for survivors, 21 months, range: 4-37 months). Forty patients (37.4%) were positive for LY MM RT-PCR and 28 (26.2%) were positive based on BL MM RT-PCR. No differences for disease-free survival (DFS) curves according to BL MM RT-PCR were observed, but we found significant differences in the estimated 24-month DFS rate for patients with at least one marker and those without any marker in lymph fluid [18.9% (95% confidence interval: 1.4-37.5%) and 42.1% (95% confidence interval: 29.7-54.5%), median: 9.9 and 15.3 months, respectively] (P=0.04). Detection of multiple markers in lymph fluid correlated with shorter DFS. Approximately 37% of lymph fluid after radical LND were positive by MM RT-PCR, which correlated significantly with early melanoma recurrences and shorter survival. The LY MM RT-PCR seems to be an effective prognostic tool for stage III melanoma patients. The MM RT-PCR analysis of single peripheral blood sample in these patients did not have additional prognostic value.

The survival benefit to patients with positive sentinel node melanoma after completion lymph node dissection may be limited to the subgroup with a primary lesion Breslow thickness greater than 1.0 and less than or equal to 4 mm (pT2-pT3).

BACKGROUND: The survival benefit of sentinel node biopsy is still controversial. The aim of our study was to assess the overall survival (OS; calculated both from the date of primary tumor excision and lymph node dissection) data from two large groups of AJCC 2002 stage-III cutaneous melanoma patients-after completion lymph node dissection (CLND after positive sentinel node biopsy) and after therapeutic LND (TLND for clinically/cytologically detected regional lymph node metastases). MATERIALS AND METHODS: We analyzed the outcomes for 544 consecutive patients, who underwent CLND (47.4%; 258 patients) or TLND (52.6%; 286 patients) at one institution between December 1994 and January 2005. There were no significant differences between the two groups in terms of age and gender distribution and in the parameters of the primary tumor. Median follow-up time was 36 months (range 6-110 months). RESULTS: We found no significant differences in OS (from the date of primary tumor excision) between CLND and TLND patients in the groups with primary tumor thicknesses of 1.0 mm or less or greater than 4.0 mm (pT1 and pT4); however, in patients with thicknesses greater than 1.0 mm and 4.0 mm or less (in subgroups pT2 and pT3), we found significantly better OS for CLND than for TLND patients-CLND: median OS not reached, 5-year OS was 57.2% (95%CI: 44.4-70.1%); TLND: median OS 42.1 months, 5-year OS was 37.9% (95%CI: 26.5-49.2%) (P = 0.0006). In the entire CLND and TLND groups, the median OS and 5-year OS rates were 60.5 months and 52.5% (95%CI: 45.6-61.5%) and 38.2 months and 39.5% (95%CI: 32.7-46.5%), respectively. Based on multivariate analysis, we have found that in the CLND group the important factors negatively influencing OS (from the date of lymphadenectomy) are: male gender, features of primary tumor (higher Breslow thickness and presence of ulceration) and features of nodal metastases (extracapsular invasion and number of involved nodes). In the TLND group, however, the negative prognostic factors are: male gender and features of nodal metastases (extracapsular invasion and number of involved nodes) without the impact of primary tumor characteristics. CONCLUSION: The results of the study demonstrate that the survival benefit after positive sentinel node biopsy with subsequent CLND is probably limited only to the subgroup of patients with primary tumor thicknesses not larger than 4 mm and not less than 1 mm when compared with lymph node dissection of palpable nodes. The primary tumor features have no impact on survival after lymphadenectomy performed for clinically involved nodes.

Different factors are responsible for predicting relapses after primary tumors resection and for imatinib treatment outcomes in gastrointestinal stromal tumors.

BACKGROUND: The development of accurate diagnostic methods in gastrointestinal stromal tumors (GISTs) and the introduction of imatinib (IM) therapy has focused attention on the factors influencing the prognosis of patients with primary lesions as well as of patients with advanced disease treated with imatinib. MATERIAL/METHODS: The clinico-pathological and genetic factors influencing disease-free survival (DFS) in 335 patients with primary CD117-immunopositive tumors (group A; calculated from primary tumor resection) and progression-free survival (PFS) in 232 metastatic/unresectable GIST patients treated with IM (group B; calculated from the start of imatinib therapy) were analyzed. RESULTS: In group A, statistically significant factors negatively influencing DFS(five-year DFS: 38%), both in univariate and multivariate analysis, were: primary tumor size >5 cm, mitotic index >5/50 HPF (high-power fields), male gender, primary tumor R1 resection or tumor rupture, non-gastric primary tumor localization. In group B, five factors negatively affecting PFS (three-year PFS: 54%) were identified, which were statistically significant both in univariate and multivariate analyses: WHO performance status >/=2, tumor genotype indicating other than exon 11 KIT mutation, high baseline pre-IM granulocyte count, mitotic index >10/50 HPF, and age <45 years at diagnosis. CONCLUSIONS: Different sets of independent biological and pathological prognostic factors were identified for the assessment of the natural course of primary GIST and for the prediction of PFS during IM therapy for advanced GIST.

Risk criteria and prognostic factors for predicting recurrences after resection of primary gastrointestinal stromal tumor.

BACKGROUND: The introduction of adjuvant imatinib in gastrointestinal stromal tumors (GISTs) raised debate over the accuracy of National Institutes of Health risk criteria and the significance of other prognostic factors in GIST. METHODS: Tumor aggressiveness and other clinicopathological factors influencing disease-free survival (DFS) were assessed in 335 patients with primary resectable CD117-immunopositive GISTs (median follow-up, 31 months after primary tumor resection) from a prospectively collected tumor registry. RESULTS: Overall median DFS was 37 months, and estimated 5-year DFS was 37.8 %. In univariate analysis, high or intermediate risk group (P < .000001), mitotic index >5/50 high-power field (P < .00001), primary tumor size >5 cm (P < .00001), nongastric primary location (P = .0001), male sex (P = .01), R1 resection/tumor rupture (P = .0003), and epithelioid cell or mixed cell pathological subtype (P = .05) negatively affected DFS. In multivariate analysis, statistically significant factors negatively influencing DFS for model 1 were mitotic index >5/50 high-power field (P = .004), primary tumor size >5 cm (P = .001), male sex (P = .003), R1 resection/tumor rupture (P = .04), and nongastric primary tumor location (P = .02), and for model 2 were high/intermediate risk primary tumor (P < .0001 and P = .008, respectively), male sex (P = .007), resection R1/tumor rupture (P = .01), and nongastric primary tumor location (P = .02). Five-year DFS for high, intermediate, and low/very low risk group was 20%, 54%, and 96%, respectively. CONCLUSIONS: The risk criteria for assessing the natural course of primary GISTs were validated, but additional independent prognostic factors-primary tumor location and sex--were also identified.

Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs).

THE PURPOSE: To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients. MATERIALS AND METHODS: We identified 232 patients in a prospectively collected Clinical GIST Registry with advanced inoperable/metastatic GIST treated with IM 400-800 mg daily (129 males and 103 females and median age 56 years). Median follow-up time was 26 months. RESULTS: The estimated 3-year progression-free survival (PFS; calculated from the date of the start of IM) was 54% and median PFS was 40.5 months. The following factors significantly and negatively influenced PFS in univariate analysis: poor baseline World Health Organization (WHO) performance status > or = 2 (P < 0.00001), tumor genotype indicating other than KIT exon 11 isoform (P = 0.005), baseline high neutrophils count (P < 0.00001), age <45 years at the diagnosis (P = 0.04), mitotic index >10/50 high-power fields (HPF) (P = 0.001), GIST histological type other than spindle-cell (P = 0.03), baseline low albumin level (P = 0.0005), low baseline hemoglobin level (P < 0.00001), and primary overtly malignant tumors (unresectable and/or metastatic lesions at presentation) (P = 0.05). We identified four factors negatively affecting PFS, statistically significant (P < 0.05) in multivariate analysis: baseline poor WHO performance status > or = 2, high baseline neutrophils count (>5 x 10(9)/l), tumor genotype indicating the presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF. CONCLUSIONS: We confirmed that many advanced GIST patients benefit from IM therapy for a prolonged time, although resistance to therapy is observed. We identified four independent biological factors influencing the PFS during long-term IM therapy.