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B B Kroon

Publications and source records attributed to B B Kroon.

At least 37 records · Page 2Linked to original sources

Reliability of sentinel lymph node biopsy for staging melanoma.

BACKGROUND: The aim of this study was to evaluate the reliability of sentinel lymph node biopsy for staging melanoma. METHODS: Two hundred consecutive patients with a cutaneous melanoma of at least 1. 0 mm Breslow thickness, without palpable regional lymph nodes, were included from 1993 in a prospective cohort study in a single tertiary care hospital. One day after lymphoscintigraphy, sentinel node biopsy was performed, guided by a gamma probe and patent blue dye. Lymph node dissection was performed only if metastasis was found in a sentinel node. Median follow-up was 32 (range 3-61) months. No patient was lost to follow-up. RESULTS: A sentinel node was removed in 199 of 200 patients (mean 2.2 nodes per patient). Forty-eight patients (24 per cent) had metastasis in a sentinel node. Fifteen patients developed recurrence after removal of a tumour-negative sentinel node; six relapsed in the previously mapped basin (false-negative rate 11 per cent (six of 54)). The overall survival at 3 years was 93 per cent if the sentinel node was negative and 67 per cent if it was positive. Sentinel node status and Breslow thickness were strong predictors of recurrence and survival. Minor complications were seen in 18 patients. CONCLUSION: The sentinel node status was a strong prognostic factor, even with a false-negative rate of 11 per cent. Published in abstract form as Eur J Nucl Med 1999; 26(Suppl): S57

Adolescent↗

High tPA-expression in primary melanoma of the limb correlates with good prognosis.

To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation (PA) system, immunohistochemical stainings for activators of plasminogen (tissue type (tPA) and urokinase type (uPA)), inhibitors of plasminogen activation (type 1 (PAI-1) and type 2 (PAI-2)) and the receptor for uPA (uPAR) were performed on 214 routinely processed melanoma lesions. All lesions were primary cutaneous melanomas, minimally 1.5 mm thick, and derived from patients with only local disease at the moment of diagnosis (clinically stage II (T(3-4)N(0)M(0)), American Joint Committee on Cancer). Median patient follow-up was 6.1 years. Single variables as immunohistochemical staining results (extent of tumour cell staining, pattern of tumour cell staining and for some components also staining of stromal cells), histopathological and clinical parameters as well as treatment variables were analysed in order to assess their prognostic importance, in terms of time to recurrence, time to distant metastasis and duration of survival. The extent of tPA tumour cell positivity, categorized as 0-5%, 6-50% and 51-100%, appeared to be of importance for these end-points. Lesions with 51-100% tPA-positive tumour cells were found to have the best prognosis, whereas lesions with 6-50% tPA-positive tumour cells had the worst. Moreover, the prognostic significance of Breslow thickness, microscopic ulceration and sex was confirmed in this study. Multivariate analyses, incorporating these relevant factors, showed that the extent of tPA tumour cell positivity was an independent prognostic factor for distant metastasis-free interval (P = 0.012) and for the duration of survival (P = 0.043).

Adolescent↗

Evaluation of mammary lymphoscintigraphy by a single intratumoral injection for sentinel node identification.

UNLABELLED: The aim of this study was to evaluate the findings of mammary lymphoscintigraphy by a single intratumoral injection in 150 patients with breast carcinoma: 100 patients (group A) investigated in the validation phase of the study and 50 (group B) studied after the tracer dose was optimized. METHODS: Immediately after injection of 99mTc-nanocolloid using a 25-gauge needle and a 0.2-mL volume, simultaneous anterior and lateral images were acquired with a dual-head gamma camera during 20 min followed by sequential static anterior and prone lateral breast images after 30 min and after 2 and 4 h. 57Co-assisted skin marking defined the sentinel node location for subsequent gamma probe, blue dye-guided sentinel node biopsy. RESULTS: In group A (mean dose, 61.6 MBq; range, 42-88 MBq) scintigraphy revealed lymph nodes in 83 patients (83%), with an increase in the rate of visualization from 72% for the first 40 patients to 90% for the last 60; patient age (P = 0.01) and administered tracer dose (P = 0.04) were found to be significant factors for visualization, with optimal results obtained from doses higher than 65 MBq. Lymph nodes were visible in 34 patients (41%) during the first 30 min after injection, whereas in 49 patients appearance occurred at 2-4 h. A total of 97 lymphatic basins were visualized (80 axillary, 3 clavicular, 14 internal mammary). In group B (mean dose, 90.8 MBq; range, 68-124 MBq), the visualization rate was 94%, with early lymph node appearance in 27 patients (57%) and a total of 53 basins (45 axillary, 8 internal mammary). In combination with intraoperative blue dye mapping and y probing, the identification rate increased to 90% in group A and 98% in group B. Prone lateral images contributed to identification of intramammary lymph nodes in a total of 14 patients and axillary nodes close to the injection site in 8 other patients. CONCLUSION: Mammary lymphoscintigraphy by single intratumoral injection is a valid method for lymphatic mapping and identification of both axillary and nonaxillary sentinel nodes. Lymph node visualization appears to be improved with higher tracer doses. The compactness of the injection site enables high-quality additional lateral images that can depict intramammary or axillary lymph nodes adjacent to the injection site.

Adult↗

Management of malignant melanoma.

The following guidelines are recommended in the management of malignant melanoma. An excisional biopsy is the appropriate diagnostic procedure for a skin lesion suspected of being a melanoma. The advised margin for diagnostic excision is 2 mm of macroscopically normal skin around the lesion; the margins for therapeutic excision are 1 cm of normal skin for a lesion with a Breslow thickness of < 2 mm and 2 cm when the Breslow thickness is > 2 and < or = 4 mm. A margin of at least 2 cm also appears to be justified for thicker melanomas. Elective lymph node dissection is not recommended. Sentinel node biopsy appears to be a promising method to detect occult metastases in the regional lymph nodes. If regional lymph node metastases are present, therapeutic regional lymph node dissection must be conducted. Isolated regional perfusion is indicated for inoperable tumour growth in an extremity. Radiotherapy can be applied palliatively or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy is still experimental. There is no standard treatment for patients with haematogenic metastasis and they should be entered in trials whenever possible. A follow-up period of 5 years is sufficient for patients with a melanoma of < or = 1.5 mm Breslow thickness and of 10 years when the Breslow thickness is > 1.5 mm. The patients should be actively involved in the follow-up (inspection, palpation). Regular routine blood tests and radiological examinations are not considered to be worthwhile. There is no evidence that the growth of micro-metastases is stimulated by hormonal changes during pregnancy or contraceptive pill use. Excessive exposure to ultraviolet radiation should be discouraged.

Adult↗

Clear cell sarcoma (malignant melanoma) of soft parts: A clinicopathologic study of 30 cases.

BACKGROUND: Clear cell sarcoma, or malignant melanoma of soft parts, is a rare tumor that occurs predominantly in the extremities of young adults. The importance of surgery has been well established. However, the role of adjuvant radiotherapy has yet to be determined. METHODS: Thirty cases of clear cell sarcoma that occurred in The Netherlands between 1978 and 1992 were studied retrospectively. Follow-up information on 29 patients was obtained; the follow-up period ranged from 4 to 241 months, with a median of 30 months. All tumors occurred in the extremities, mostly of young adults. RESULTS: The 5-year survival rate of the 29 patients was 54%. For the 23 patients who presented with localized disease, the 5-year survival and 5-year disease free survival were 65%. Eleven of these patients remained disease free after resection of the primary tumor. Patients with a tumor 2 cm or smaller had better survival than patients with a larger but still-localized tumor (P = 0.009). Adjuvant radiotherapy to the primary tumor site also seemed to have a beneficial effect on survival (P = 0.036). All patients with a local recurrence (8 patients) or regional lymph node metastasis (13 patients) developed distant metastasis. Fourteen of 18 patients with distant spread died of their disease; 2 patients were still alive with disease and 2 patients were disease free, 7 and 32 months after resection of solitary distant metastases. CONCLUSIONS: Early diagnosis and initial radical surgery are essential for a favorable outcome. Once regional lymph node metastasis or hematogenous dissemination has occurred, the prognosis is dismal.

Adolescent↗

Low risk of locoregional recurrence of primary breast carcinoma after treatment with a modification of the Halsted radical mastectomy and selective use of radiotherapy.

BACKGROUND: The purpose of the current study was to evaluate the locoregional recurrence rate after treatment of patients with operable breast carcinoma with a modification of the Halsted radical mastectomy and the selective use of radiotherapy and to identify risk factors for locoregional recurrence. METHODS: Between 1979-1987, 691 consecutive patients underwent mastectomy after a negative biopsy of the axillary apical lymph nodes. The median age of the patients was 59 years (range, 26-89 years). The clinical tumor size was < 2 cm in 72 patients, 2-5 cm in 387 patients, and >5 cm in 169 patients; 16 patients had a T4 tumor. Surgery was comprised of a modification of the Halsted radical mastectomy, including at least part of the pectoralis major muscle and the entire pectoralis minor muscle, in 573 patients; 303 patients had positive axillary lymph nodes. Adjuvant radiotherapy to the chest wall and regional lymph nodes was given to 74 patients, whereas an additional 414 patients underwent irradiation to the internal mammary and medial supraclavicular lymph nodes. The median follow-up was 91 months. RESULTS: The actuarial overall survival rate was 82% at 5 years and 63% at 10 years. The 10-year chest wall and regional lymph node control rates, including patients with prior distant failures, were 95% and 94%, respectively. The only two significant prognostic factors for locoregional recurrence on multivariate analysis were lymph node status and pathologic tumor size. CONCLUSIONS: Excellent locoregional control can be achieved with a modified technique of radical mastectomy in patients with negative apical biopsy and the selective use of comprehensive radiotherapy. These results may serve as a reference outcome for comparison with other locoregional treatment strategies.

Adult↗

Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNF-alpha), interferon gamma, and melphalan has proved to be useful in the treatment of recurrent malignant melanoma and of locally advanced soft tissue sarcomas of the extremities. OBJECTIVE: To determine whether this modality is also effective in the treatment of locally advanced nonmelanoma skin tumors of the extremities. PATIENTS AND METHODS: Fifteen patients with locally advanced primary, recurrent, or metastatic skin tumors of the extremities (12 with squamous cell carcinoma and 3 with Merkel cell carcinoma) underwent HILP with TNF-alpha, interferon gamma, and melphalan. Six tumors were localized in the upper extremity (40%), and 9 in the lower extremity (60%). Treatment-related complications, limb salvage rate, local recurrence, and regional and distant metastases were scored during a median follow-up of 20 months. RESULTS: After HILP, 9 patients (60%) showed a complete response (with histopathological confirmation). Four patients (27%) showed a partial response (with histopathological confirmation in 1 patient), and 2 patients (13%) showed no change (with histopathological confirmation in 1 patient and with clinical evidence in 1 patient). Two patients (13%) showed treatment-related complications. The limb salvage was achieved in 12 patients (80%), and the local recurrences developed in 4 patients (27%). During follow-up, regional lymph node metastases were observed in 2 patients (13%) and distant metastases in 2 patients (13%). CONCLUSION: Based on our results, HILP with TNF-alpha, interferon gamma, and melphalan should be considered as a limb-saving treatment modality in patients with locally advanced nonmelanoma skin tumors of the extremities who would otherwise be candidates for ablative surgery.

Adult↗

Lymphoscintigraphy in oncology: a rediscovered challenge.

The validation of the sentinel node concept in oncology has led to the rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping with intraoperative probe detection this nuclear medicine procedure is being increasingly used to identify and detect the sentinel node in melanoma, breast cancer, and in other malignancies such as penile cancer and vulvar cancer. In the past lymphoscintigraphy has been widely applied for various indications in oncology, and in the case of the internal mammary lymph-node chain its current use in breast cancer remains essential to adjust irradiation treatment to the individual findings of each patient. In another diagnostic area, lymphoscintigraphy is also useful to document altered drainage patterns after surgery and/or radiotherapy; its use in breast cancer patients with upper limb oedema after axillary lymph-node dissection or in melanoma patients with lower-extremity oedema after groin dissection can provide information for physiotherapy or reconstructive surgery. Finally, the renewed interest in lymphoscintigraphy in oncology has led not only to the rediscovery of findings from old literature reports, but also to a discussion about methodological aspects such as tracer characteristics, image acquisition or administration routes, as well as to discussion on the study of migration patterns of radiolabelled colloid particles in the context of cancer dissemination. All this makes the need for standardized guidelines for lymphoscintigraphy mandatory.

Breast Neoplasms↗

Lymphatic mapping and sentinel lymph node biopsy in breast cancer.

Lymphatic mapping with selective lymphadenectomy is an attractive approach in breast-cancer patients. It uses existing technology to exploit logical anatomic and physiological principles to identify occult regional lymph-node metastases. The lymphatic flow is visualized and the first (sentinel) lymph node on a direct drainage pathway from the primary tumour is identified. This is the node at greatest risk of harbouring metastatic deposits. Retrieving this node requires a concerted effort from the nuclear medicine physician, surgeon and pathologist. Lymphoscintigraphy can indicate the number of sentinel nodes and their location. The surgeon can use two techniques to find the node. A vital dye injected at the tumour site will stain the lymphatic duct as well as the sentinel node and allow their visual identification. Alternatively, a lymph-node-seeking radiopharmaceutical will also migrate from the tumour site to the sentinel node and will enable its retrieval with the use of a gamma detection probe. The pathologist has a number of techniques to identify tumour deposits in the lymph node. A review of the literature shows that the sentinel node can be found in more than 90% of the patients. With experience, the false-negative rate can be kept down to about 5%. This novel approach of lymphatic mapping with selective lymphadenectomy may lead to a substantial reduction in the need for axillary node dissection in patients with breast cancer without compromising survival and regional control, and without loss of prognostic and staging information. This development will translate into a great reduction in patient morbidity and medical expenses.

Breast Neoplasms↗

Absence of severe systemic toxicity after leakage-controlled isolated limb perfusion with tumor necrosis factor-alpha and melphalan.

BACKGROUND: Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation. METHODS: Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes. RESULTS: Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients. CONCLUSIONS: Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.

Adult↗

Relation between limb toxicity and treatment outcomes after isolated limb perfusion for recurrent melanoma.

BACKGROUND: The optimal toxic reaction of the normal tissues in perfused limbs after isolated limb perfusion (ILP) is unknown. Theoretically, more severe limb toxicity could reflect a concomitant increased toxic effect to the tumor and improved outcomes. We determined whether there is a relation between limb toxicity and treatment outcomes after ILP for recurrent limb melanoma. STUDY DESIGN: Among 252 patients with recurrent melanoma of the limbs, treatment outcomes in 192 patients (76%) with no or mild acute limb toxicity were compared with those in 60 (24%) with more severe reactions. Multivariate analysis was used to identify prognostic factors for complete response, limb recurrence-free interval, and survival. RESULTS: Among 112 patients with measurable disease, 65 patients (58%) had a complete response and 27 (42%) experienced a relapse in the perfused limb. For complete response, uninvolved regional lymph nodes (p = 0.0025) and ILP using tumor necrosis factor-alpha (p = 0.0076) appeared to be favorable prognostic factors in multivariate analysis. There was no evidence of a relation between limb toxicity and complete response either in univariate (p = 0.16) or multivariate analysis (p = 0.46). For limb recurrent-free interval, only the number of lesions was a significant prognostic factor (p = 0.047); limb toxicity was not (p = 0.095). In 140 patients with recurrent melanoma excised before or at the moment of ILP, independent prognostic factors for survival were gender, the number of positive nodes, and stage of disease. There was no relation between limb toxicity and survival in either univariate (p = 0.53) or multivariate analysis (p = 0.94). Forty-eight (34%) of the 140 patients had a relapse in the perfused limb. No prognostic factors for limb recurrent-free interval could be identified; limb toxicity was not related to relapse time in univariate or multivariate analyses (p = 0.16 and p = 0.14, respectively). CONCLUSIONS: More severe acute limb toxicity is not associated with improved outcomes. One should aim at grade II toxicity (slight erythema or edema, compatible with complete recovery) at the most to increase the therapeutic ratio of ILP.

Adolescent↗

Long-term functional morbidity after mild hyperthermic isolated limb perfusion with melphalan.

AIMS: To assess long-term functional morbidity in patients entered in the prospective randomized EORTC trial investigating the role of adjuvant isolated limb perfusion (ILP) with melphalan for high-risk primary melanoma. METHODS: In 65 patients (ILP 36, wide excision only 29), limb circumference and joint mobility measurements were performed on the treated and the contralateral limb after a mean interval of 48 months after primary treatment. The two treatment groups were comparable regarding age, sex distribution, percentage of skin grafts or regional lymph-node dissections, and interval between primary treatment and physical measurements. RESULTS: None of the patients had severe complaints of the treated limb at the time of analysis. The ankle suffered most from ILP, with a statistical significant restricted extension in approximately 40% of the perfused patients. Abduction of the shoulder was minimally affected in treated upper limbs, probably as a result from the formation of scar tissue after axillary lymph-node dissection. Although no significant differences could be demonstrated in the circumference of upper or lower limbs, atrophy was seen in 24% of perfused lower limbs. Of the five perfused patients who developed oedema, four had also undergone a regional lymph-node dissection. CONCLUSION: This risk of long-term functional morbidity should be weighed against the possible advantages of ILP in patients with limb melanoma or sarcoma.

Adolescent↗

Consensus on the management of malignant melanoma of the skin in The Netherlands. Dutch Melanoma Working Party.

In 1996 the Dutch Melanoma Working Party, in co-operation with the National Organization for Quality Assurance in Hospitals in the Netherlands and the Dutch Association of Comprehensive Cancer Centres, organized the third consensus conference on the management of melanoma of the skin. The following guidelines were approved. The recommended margin for diagnostic excision is 2 mm of macroscopically normal skin around the lesion; the margins for therapeutic excision are 1 cm of normal skin for a Breslow thickness of < or = 2 mm and 2 cm for a Breslow thickness of > 2 and < or = 4 mm. A margin of at least 2 cm also appears to be justified for thicker melanomas. Elective lymph node dissection is not recommended. Sentinel node biopsy appears to be a promising method to detect occult metastases in the regional lymph nodes. If regional lymph node metastases are present, therapeutic regional lymph node dissection must be conducted. Isolated regional perfusion is indicated for inoperable tumour growth in an extremity. Radiotherapy can be applied curatively (for example, if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy for melanoma patients is still experimental. Atypical (dysplastic) naevi and congenital naevi are major risk factors for melanoma. No consensus has been reached about the prophylactic excision of all congenital naevi. A follow-up period of 5 years is sufficient for patients with a melanoma of < or = 1.5 mm Breslow thickness (provided there are no histological signs of regression) and of 10 years when the Breslow thickness is > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Regular routine blood tests, radiological examination and ultrasound scanning are not considered to be worthwhile. There is no evidence that the growth of micro-metastases is stimulated by hormonal changes during pregnancy or contraceptive pill use. Excessive exposure to ultraviolet radiation should be discouraged. Regular population screening for melanoma is not considered to be worthwhile, owing to the relatively low frequency and the predominantly favourable stage at the time of diagnosis, particularly in young people.

Diagnosis↗

Hyperthermic isolated limb perfusion with tumour necrosis factor and melphalan as treatment of locally advanced or recurrent soft tissue sarcomas of the extremities.

Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents has been used for the local treatment of high-grade soft tissue sarcomas (STS) of the extremities, but in most cases with a disappointing result. Most regimens should certainly not be considered superior to surgery plus radiotherapy. Although the majority of extremity STS can be resected locally, some have a very large size and are in close proximity to bones, nerves or blood vessels. In these cases, amputation is the only means of resecting the tumour. A new combination of drugs used in the set-up of HILP with tumour necrosis factor-alpha and melphalan has emerged as a very promising option for the limb-saving management of locally advanced STS. In recent studies, complete response rates of approximately 30% and partial remission rates of 50% have been achieved, while the overall limb-salvage rate is more than 80%.

Antineoplastic Agents, Alkylating↗

Vascular complications of isolated limb perfusion.

AIM: Isolated limb perfusion (ILP) is a complex vascular procedure which uses an extracorporeal circuit with high doses of cytostatic drugs and often hyperthermia for the treatment of extremity tumours. Our study investigated the incidence, treatment and subsequent outcome of vascular complications after ILP, about which little is known. METHODS: A retrospective study was performed, in which we found 10 vascular complications after 466 ILPs (2.1%). RESULTS: In eight patients, acute arterial obstruction developed in the immediate post-operative period, resulting from a thrombus at the arteriotomy site. Prompt reintervention with thrombectomy restored the circulation in all patients. One patient developed an arterial thrombus in the brachial artery due to compression of the surrounding tumour 12 days after ILP, which was successfully treated with thrombectomy and freeing the artery from the tumour. One patient was treated conservatively for digital micro-emboli. All complications occurred in women, maybe because of their generally smaller vessel size. No limbs were lost and all patients were free of any vascular problem after a median follow-up of 3.6 years. CONCLUSIONS: We conclude that vascular complications after ILP are rare, consist mainly of thrombosis at the arteriotomy site and can be successfully treated by prompt thrombectomy. Therefore, close observation of the peripheral circulation after ILP is necessary.

Adult↗

Cervical lymph-node metastasis from cutaneous melanoma of the head and neck: a search for prognostic factors.

AIMS: To identify prognostic factors determining overall survival in patients with surgically treated neck node metastases of cutaneous melanoma. METHODS: A retrospective study was carried out in 70 patients who were surgically treated with curative intent for cervical lymph-node metastasis from cutaneous head and neck melanoma at our institution between 1960 and 1986. RESULTS: Median follow-up of the 14 patients still alive was 10 years. Of the 70 patients, 64 underwent a radical neck dissection, four a modified radical neck dissection and two a postero-lateral neck dissection. In 63 patients, the node dissection was for palpable involved nodes and in seven for microscopic disease. Survivals after 5 and 10 years were 23% (SE 5%) and 20% (SE 5%), respectively. Five-year survival was 62% (SE 17%) for patients with a melanoma less than 1.5 mm thick and 16% for lesions thicker than 1.5 mm. A regional recurrence in the neck occurred in 16 (23%) patients, of whom 14 were found also to have distant metastases. All patients with regional recurrence died from disease. CONCLUSIONS: Of the 15 patient-, tumour- and treatment-related factors tested, only the Breslow thickness of the primary lesion carried prognostic significance for survival (Bonferroni corrected P-value: 0.026).

Adolescent↗