Jens Baumert

Response to Neoadjuvant Chemotherapy Combined With Regional Hyperthermia Predicts Long-Term Survival for Adult Patients With Retroperitoneal and Visceral High-Risk Soft Tissue Sarcomas

PURPOSEnTo determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS).nnnPATIENTS AND METHODSnFrom 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation.nnnRESULTSnObjective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy.nnnCONCLUSIONnResponse to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.

Risk of second primary malignancies in patients with cutaneous melanoma

Backgroundu2003In several studies an increased risk for development of breast cancer, malignant lymphoma and neoplasms of the kidney as second primary cancers in patients with cutaneous melanomas was discussed.

Delay in the diagnosis of cutaneous melanoma: an analysis of 233 patients

Knowledge of factors associated with the detection of cutaneous malignant melanomas and reasons for delay in diagnosis are essential for the improvement of secondary prevention of cutaneous melanoma. For this reason, the extent and consequence of patient and professional delay in diagnosis and treatment was investigated in 233 patients with histologically proven primary cutaneous melanomas seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University, Munich, Germany, between January 1999 and January 2001. Personal interviews were conducted by two physicians to obtain information on patients’ knowledge of melanoma symptoms, sun behaviour, delay in seeking medical attention, professional delay and related factors. The main component of delay was patient related. Nearly one-third (29.2%) of all patients reported a delay interval of more than 12 months from the onset of an observed change in a pigmented lesion or first detection of a pigmented lesion to the first visit to a physician. The delay interval from the first visit to a physician to surgical treatment was shorter (< 1 month) in most of our patients (74.7%). The predominant symptoms of melanoma detected by patients were a change in colour and an increase in size or elevation. Most patients had obtained knowledge about cutaneous melanomas from television and magazines. A delay in diagnosis and a history of many sunburns and outdoor leisure time activities were not associated with a greater tumour thickness. However, fairer skin types, lower education levels and lack of knowledge about cutaneous melanoma were associated with a greater tumour thickness. Further efforts are necessary to improve public and medical education about early detection and prompt surgical treatment, which is known to be the most effective treatment modality for cutaneous melanomas.

Factors associated with a high tumour thickness in patients with melanoma.

Backgroundu2002 Prognosis of patients with melanoma is strongly associated with tumour thickness at time of diagnosis. Therefore, knowledge of patient characteristics and behaviour associated with a high tumour thickness is essential for the development and improvement of melanoma prevention campaigns.

Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia☆

The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44-73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.

Disease progression in patients with thin cutaneous melanomas (tumour thickness ≤ 0·75 mm): clinical and epidemiological data from the Tumour Center Munich 1977–98

Backgroundu2003 Although survival in patients with thin melanomas (tumour thickness ≤u200a0·75u2003mm) is usually excellent, thin melanomas have the potential to metastasize.

Prognostic index for cutaneous melanoma: an analysis after follow-up of 2715 patients.

In 2715 of 4524 patients with cutaneous melanoma treated surgically between 1968 and 1992 prognostic parameters were analysed for their value in predicting the occurrence of first progression. All of the 2715 patients developed only one invasive cutaneous melanoma during the follow-up period. Data concerning tumour thickness and mitotic index (maximum number of mitoses per square millimetre) of the cutaneous melanomas were determined. Between the characteristics age, tumour thickness, mitotic index, prognostic index (PI), sex, site of tumour, melanoma subtype and Clark level, the value of the mitotic index, as a prognostic parameter independent of tumour thickness, and the combination of mitotic index and tumour thickness were evaluated. The development of the first metastases was documented during a mean follow-up of 7.5 years. The majority of first recurrences occurred at regional lymph nodes and attempts have been made to identify those patients at risk of developing metastatic disease. The most effective parameters proved to be tumour thickness and mitotic index. For both parameters an independent prognostic influence was shown. The prognostic index, defined as the product of tumour thickness and number of mitoses per square millimetre, was re-evaluated and confirmed. A new modified prognostic index, defined as the product of square tumour thickness and mitotic index, proved to be even more useful for defining a subgroup of patients who are at risk of developing metastases and, therefore, might benefit from adjuvant therapy.

The Use of High‐Resolution Ultrasonography for Preoperative Detection of Metastases in Sentinel Lymph Nodes of Patients with Cutaneous Melanoma

BACKGROUND Sentinel lymph node biopsy (SLNB) reliably assesses the status of the regional lymph node basins and provides prognostic information in patients with cutaneous melanoma, but is logistically demanding and expensive. OBJECTIVE The aim of this study was to evaluate the ability of high resolution B‐mode ultrasonography (US) for pre‐operative identification and characterization of sentinel lymph nodes (SLN) in patients with cutaneous melanoma. PATIENTS AND METHODS In a prospective trial, the use of high resolution US was assessed in 25 consecutive patients with cutaneous melanoma identified for SLNB, first, for its value in primary detection of SLN, and, second, for its value in the correct assessment of SLN after lymphoscintigraphic mapping. RESULTS High resolution B‐mode US correctly identified two of 6 positive SLN. The sensitivity, specificity, positive predictive value, and negative predictive value of US were 33.3% (95% CI 43.3–77.7), 100.0% (95% CI 88.1–100.0), 100.0% (95%CI 15.8–100.0) and 87.9% (95% CI 71.8–96.6), respectively. CONCLUSION High resolution B‐mode US cannot replace SLNB, especially in the detection of micrometastases, but it remains the most important method to assess the lymph node status for macrometastases presurgically. The authors have indicated no significant interest with commercial supporters.

Characteristics associated with low treatment satisfaction in patients with implanted cardioverter defibrillators: results from the LICAD study.

The evaluation of low treatment satisfaction (LTS) with an implanted cardioverter defibrillator (ICD) remains a neglected area of clinical research. However, a trustful attitude toward an ICD is crucial. Within the scope of ICD health technology assessment, we searched for predictors of LTS. Of 195 ICD patients enrolled (mean 59.8 years, standard deviation 12.6), 163 (83.6%) were men and 26 (16.4%) were women. We measured anxiety, helplessness, and depression with standardized instruments and LTS with 11 dichotomous items concerning a mistrustful attitude, a negative body image, and low appraisal. A total of 47 (24.1%) patients were considered as LTS patients. Multivariate logistic regression was used for assessment of LTS. Adjusted for age and survey, LTS was significantly more prevalent in depressed, anxious, and phobic patients. Multivariate logistic regression including medical and psychological covariates revealed the experience of ≥5 shocks with an odds ratio (OR) of 10.17 (95% CI 3.57–29.00, P ≤ 0.001), being employed with an OR of 8.07 (95% CI 2.39–27.19, P ≤ 0.001), and feelings of helplessness (OR 4.61, 95% CI 1.79–11.90, P ≤ 0.002) as the most important predictors for LTS. Women had a slightly not significant effect on LTS. Age, educational status, and depression were not significant. LTS patients required more support for living with the ICD (P ≤ 0.001). Thus, LTS serves as surrogate measure for deteriorated psychic health. Clinicians should be advised to identify LTS patients and to consider psychotherapeutic counseling for them.

Analysis of predictive factors for the outcome of complete lymph node dissection in melanoma patients with metastatic sentinel lymph nodes

BACKGROUNDnSentinel lymph node biopsy (SLNB) is a widely accepted procedure to accurately stage patients with melanoma. However, there is no consensus concerning the practical consequences of a positive SLN, since a survival benefit of a complete lymph node dissection (CLND) has not yet been demonstrated.nnnOBJECTIVEnWe wondered whether we could identify a subgroup of patients with metastatic involvement of the SLN who could be excluded from the recommendation to undergo CLND.nnnMETHODSnAt the Department of Dermatology at the University of Munich, a total of 213 patients with metastatic SLNs (24.9%) were identified among 854 patients who had undergone SLNB between 1996 and 2007. All SLN-positive patients had been advised to have CLND. Survival analyses were performed by using the Kaplan-Meier approach.nnnRESULTSnA total of 176 (82.6%) of 213 SLN-positive patients underwent CLND. In this group, 26 patients (14.8%) showed metastatic disease in non-sentinel lymph nodes (NSLN). The 5-year overall survival (OS) was 26.1% in NSLN-positive patients and 74% in NSLN-negative patients. SLN-positive patients who refused CLND had a better prognosis than patients with CLND. Breslow tumor thickness was significantly associated with positive CLND status with higher median values in CLND-positive than CLND-negative patients (3.03 vs 2.22 mm).nnnLIMITATIONSnThe subgroup of patients with metastatic disease in CLND may have been too small to reach statistical significance for other tumor- or patient-related parameters. Mitotic indices of the primary melanomas had not been determined in this retrospective study; thus a possible correlation with lymph node status could not be tested.nnnCONCLUSIONnAmong SLN-positive patients, the presence of metastatic NSLN is a highly significant poor prognostic factor. Tumor thickness is a significant prognostic parameter for positive CLND status and might be considered in the decision to perform CLND in case of metastatic SLN.