Purpose: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen.Experimental Design: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625).Results: Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment.Conclusions: TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2.

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This case-control study assesses the association of hydrochlorothiazide with risk of malignant melanoma among Danish adults.

Epidemiologic data on local complications after breast augmentation are scarce. In particular, few prospectively collected data are available on modern breast implants on this issue. Using data from the Danish Registry for Plastic Surgery of the Breast, the authors examined determinants of surgery-requiring complications and capsular contracture grades III to IV among 2277 women who underwent cosmetic breast implantation from June 1999 through April 2003. During an average follow-up period of 1.6 years after implantation, 4.3% of these women (3% of implants) required secondary surgery as a result of short-term complications. The most frequent clinical indications for surgery were displacement of the implant (38%), capsular contracture grades III to IV (16%), ptosis (13%), and hematoma (11%). Overall, the authors found that inframammary incision and subglandular placement were associated with decreased risks of developing complications requiring surgical intervention, whereas implants larger than 350 mL increased the risk of such complications (relative risk [RR], 2.3; 95% confidence interval [CI], 1.3-4.0). Thirty-nine Baker III to IV capsular contractures were identified, of which 22 were treated surgically within the study period. Submuscular placement of the implant decreased the risk of capsular contracture grades III to IV (RR, 0.3; 95% CI, 0.2-0.8), whereas surgical routes other than inframammary and drainage of implant cavity were associated with increased risk of capsular contracture. Current surgical practices and modern implants used for breast augmentation produce fewer short-term complications than procedures and devices of the past. This prospective study indicates that surgical procedures are more important predictors for local (short-term) complications than implant or patient characteristics.