Additional Systemic Therapy Research Articles

The current status of image-guided external beam radiotherapy for prostate cancer

To assess the current status and technological advances in image-guided external beam radiotherapy for prostate cancer. Modern imaging has improved the ability to define radiotherapy target volumes. Specifically, treatment margins have been reduced through the use of treatment planning and image-guidance technology. Increasing dose has led to increased disease control. Concurrent technological advances may improve treatment-related toxicity. Data continues to emerge on patient selection, treatment schedule, and use of additional systemic therapy in conjunction with radiation. In the present article, we review recent developments in radiation planning, image guidance, patient selection and fractionation, dose escalation, toxicity, systemic therapy, and follow-up.

Abstract 5639: Preoperative concurrent paclitaxel and radiation in locally advanced breast cancer (LABC): Five-year outcomes on 105 patients

Abstract Purpose: A prospective trial of preoperative concurrent paclitaxel and radiation for patients with LABC was conducted at three academic institutions. Five-year local and systemic control rates are reported. Patients and Methods: 105 patients with LABC were treated with concurrent neoadjuvant paclitaxel and radiation. Paclitaxel was administered at 30 mg/m2 intravenously twice a week for 10-12 weeks. Daily radiotherapy was delivered to the breast, axillary and supraclavicular lymph nodes during weeks 2-7, at 1.8 Gy per fraction to a total dose of 45 Gy followed by a boost of 14 Gy at 2 Gy per fraction to the originally palpable tumor. Weekly trastuzumab (2mg/kg) was added for 8 more recent patients whose tumor over-expressed Her-2/neu. At one of the three institutions preoperative paclitaxel (3 cycles of 175 mg/m2 q 3 weeks) was also administered prior to chemo-radiation to 36 patients. Pathologic response was defined as complete response (pCR) in the absence of invasive cancer in breast or lymph nodes; partial response (pPR) as the persistence of < 10 microscopic foci of invasive carcinoma in breast or lymph nodes. After surgery additional systemic therapy was left to the discretion of the treating physician. Results: Pathological response (pCR and pPR) after neoadjuvant chemo-radiation was achieved in 36/105 patients (34.3%, 95% confidence interval: 25.3% - 44.2%). 30/105 patients underwent breast-conserving surgery after neoadjuvant chemo-radiation (28.6%), while 74 underwent mastectomy. One patient progressed during therapy and did not undergo surgery. With a median follow up of 60 months and a maximum of 137 months, the median survival has not been reached. The estimated 5-year overall cumulative survival (OS) is 71.6% (95% confidence interval: 60.5% - 80.1%). Local recurrence occurred in 4/105 patients (3.8%): in 3/4 synchronously with or following systemic recurrence. Five patients (4.8%) developed contra-lateral breast cancer. Patients without a pathologic response had a higher risk of recurrence or death than patients who had a pathologic response (hazard ratio = 2.86, logrank p-value=0.009); similarly, survival was shorter (hazard ratio = 4.28, logrank p-value=0.003). The 5-year estimated OS for non-responders was 61.6% compared with 87.9% for responders. A separate analysis of patients who received additional preoperative paclitaxel before chemo-radiation showed a pathologic response rate of 41.7% (15/36 patients, 95% confidence interval: 25.5% to 59.2%); with an estimated 5-year OS of 63.9% (95% confidence interval: 46.1% - 77.2%). Conclusion: This series of 105 patients with LABC treated with concurrent paclitaxel and radiation demonstrated a 71.6% 5-year OS and 96% local control rate. Pathological response to concurrent paclitaxel and radiation was associated with a significantly better 5-year survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5639.

Nodal-Stage Classification in Invasive Lobular Breast Carcinoma: Influence of Different Interpretations of the pTNM Classification

PURPOSE Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. PATIENTS AND METHODS SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. CONCLUSION Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy.

Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.

Breast cancer in a BRCA2 mutation carrier with a history of prostate cancer

A 49-year-old patient with high-risk prostate cancer presented to a specialist. He was treated with neoadjuvant hormonal therapy for 6 months, followed by conformal radiotherapy. Three years later, he had a biochemical recurrence and commenced continuous luteinizing hormone-releasing hormone analog and antiandrogen therapy as part of a clinical trial. Aside from notable gynecomastia, he remained asymptomatic. He has a strong family history of breast cancer with multiple sisters affected. At 58 years of age, the patient underwent BRCA2 germline testing and was found to be a mutation carrier. Following post-test counseling, he was offered clinical breast examination, which was unremarkable except for gynecomastia. Baseline screening mammography identified a 4 mm cluster of microcalcifications and ductal carcinoma in situ (DCIS) was confirmed by stereotactic biopsy. DCIS in a male BRCA2 mutation carrier undergoing androgen deprivation therapy for prostate cancer. The patient was treated with bilateral mastectomy and no additional systemic therapy was recommended. This case report illustrates the importance of implementing screening mammography in male BRCA mutation carriers, particularly in those with a BRCA2 mutation.

Pitfalls in sentinel lymph node biopsy

Sentinel lymph node (SLN) biopsy is a common procedure to avoid unnecessary axillary lymph node dissection in breast cancer patients with negative nodes. However, there are some problems with SLN biopsy. One is the identification rate of SLNs. Many reports showed that the rate is higher with the combined dye and gamma probe-guided method than with the dye-guided method alone. Nevertheless, with the combined method, around 5% of SLNs cannot be identified. In this issue, Ando et al. studied the axillary arch consisting of a muscular anomaly. They reported the usefulness of multidetector row computed tomography (MDCT) for an anatomical diagnosis of the axillary arch that affected SLD identification. Rokutanda et al. also reported a case of retromammary lymph node metastasis with a false-negative SLN biopsy. We have to keep in mind these anatomical varieties for SLN biopsy. The other important point is the existence of false-negative SLNs. Takei et al. gave us one of the answers to this problem. They showed that an intraoperative false-negative SLN biopsy did not affect the recurrence-free survival rate of breast cancer patients. They also showed the necessity of additional axillary radiotherapy or adjuvant systemic therapy. Nakashima et al. showed that abnormal accumulation of the radiotracer close to the radioactive spot indicates lymph node metastasis surrounding radioactive SLNs. They recommended additional lymph node biopsy surrounding radioactive SLNs. We have to continue searching for the best method for SLN biopsies for patients with breast cancer.

Comparison of cisplatin (CDDP) and radiation (RT) to cetuximab (C) and RT for locally advanced head and neck cancer (LAHNC): A preliminary analysis

6042 Background: Both concurrent CDDP/RT and C/RT have been shown in randomized trials to yield superior disease control compared to RT alone in LAHNC, but no randomized trial has compared them. We evaluated our center's experience with these regimens. Methods: From 3/1/06 - 4/1/08, 175 patients were retrospectively identified who received definitive treatment for LAHNC with CDDP (planned total dose 100 mg/m2 Q3 weeks X 3) and RT (n = 125) or C (400 mg/m2 load; 250 mg/m2 weekly) and RT (n = 50). Patients who received prior RT, additional systemic therapy, and/or surgery to the primary site were excluded. C was given for the following reasons: auditory 30%, renal 4%, cardiac 2%, performance status 18%, patient choice 16%, neuropathy 4%, unknown 2%, and a combination of factors 24%. The median age: CDDP group 56, 6% >71; C group 66.5, 40% >71. Additional CDDP and C features: male sex, 86 v 78%; stage IV, 70 v 68%; and oropharynx, 78 v 70%. Median RT dose (70 Gy), RT length (46 days), and Karnofsky performance status (KPS) (90%) were the same; alcohol/tobacco use was similar. Results: At a median follow up of 18.7 months, with death without local failure (LF) as a competing risk, the 18 month LF incidence rate was 2.5% in the CDDP group and 43.3% in the C group (p < 0.0001), with the latest event occurring at 16.5 months. The 18 month disease-free survival (DFS) and overall survival (OS) rates were 85.7 v 40.9%, and 96.8 v 73.1%, in favor of CDDP (p < 0.0001 for both). Initially, 21 variables were assessed for significance, and when Cox proportional hazards model was used for multivariate analysis to address prognostic imbalances, treatment with CDDP still predicted for improved LF, DFS, and OS (p < 0.0001 for LF and DFS; p = 0.0017 for OS). For OS analysis, the concordance probability estimates were .67 for using drug choice alone and .80 for using drug choice, T stage, RT dose, and KPS. Conclusions: CDDP/RT and C/RT were used to treat somewhat different populations with LAHNC. The observed superiority of CDDP/RT compared to C/RT in LF, DFS, and OS may reflect patient selection issues. However, preliminary multivariate modeling suggests that CDDP/RT remains the preferred option for fit patients pending further analyses and prospective studies comparing these regimens. [Table: see text]

Feasibility Trial of Partial Breast Irradiation With Concurrent Dose-Dense Doxorubicin and Cyclophosphamide in Early-Stage Breast Cancer

Anthracyclines and concurrent whole-breast irradiation result in prohibitive cutaneous toxicity. We hypothesized that anthracycline-based chemotherapy and concurrent partial breast irradiation (PBI) is safe and conducted a single-arm feasibility trial testing this hypothesis with dose-dense doxorubicin and cyclophosphamide (ddAC). Women with T1-2, N0-1 breast cancer with > or = 3 mm lumpectomy margins received PBI (40.5 Gy, 15 daily 2.7-Gy fractions) concurrently with the first two of four cycles of ddAC (60 and 600 mg/m2 of doxorubicin and cyclophosphamide, respectively, every 14 days with colony-stimulating support). Primary end points were local and systemic toxicity. Additional systemic therapy was given at the physician's discretion. Twenty-seven patients enrolled between November 2004 and January 2007, but two patients did not receive protocol therapy (one found with additional local disease and one withdrew consent). Twenty-five women completed all planned PBI. Four (16%) of 25 did not complete all ddAC (febrile neutropenia [FN], n = 2; diverticulitis and neutropenia, n = 1; and social/economic reasons, n = 1). Four among the remaining 21 who completed all ddAC had a cycle delayed (FN, n = 1; acute respiratory illness, n = 1; foot blisters, n = 1; perianal dermatitis, n = 1). There was no grade 3 to 4 anemia or thrombocytopenia. Grade 3 nonhematologic toxicities (none grade 4) occurred in 28% (seven of 25) of patients (nausea/vomiting, n = 3; stomatitis, n = 2; contralateral breast abscess, n = 1; fatigue, n = 1; and cough/bronchospasms, n = 1). The observed rate of > or = grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%). PBI with concurrent ddAC is feasible, and local/systemic toxicity is acceptable. Larger studies are warranted to assess long-term locoregional control and late toxicities.

Infantile Hemangiomas With Unusually Prolonged Growth Phase

Most infantile hemangiomas (IHs) complete their proliferative growth phase before 9 months of age, but those with unusually prolonged growth create unique clinical challenges. We performed a retrospective case series of IHs with prolonged growth to further characterize these lesions and their treatment. We identified 23 patients as having IHs with prolonged growth after 9 months of age, with growth to a mean age of 17 months. All of the IHs had a deep dermal to subcutaneous component, all had either segmental or indeterminate morphologic characteristics, and 39% involved the parotid gland. A total of 20 of 23 received prolonged treatment with systemic corticosteroids (mean duration of treatment, 11 months), and 9 of 20 received additional systemic therapies (vincristine sulfate and/or interferon alfa-2a or alfa-2b). Prolonged growth was observed primarily in IHs with a deep component and segmental morphologic characteristics. Recognition of this subset of hemangiomas is important for clinicians, and further study of IHs may provide clues to their pathogenesis.

Predicting Systemic Disease in Patients With Esophageal Cancer After Esophagectomy

The aim of this study was to determine whether the risk of systemic disease after esophagectomy can be predicted by the number of involved lymph nodes. Primary esophagectomy is curative in some but not all patients with esophageal cancer. Identification of patients at high risk for systemic disease would allow selective use of additional systemic therapy. This study is a multinational, retrospective review of patients treated with resection alone to assess the impact of the number of involved lymph nodes on the probability of systemic disease. The study population included 1,053 patients with esophageal cancer (700 adenocarcinoma, 353 squamous carcinoma) who underwent R0 esophagectomy with > or =15 lymph nodes resected at 9 international centers: Asia (1), Europe (5), and United States (3). To ensure a minimum potential follow-up of 5 years, only patients who had esophagectomy before October 2002 were included. Patients treated with neoadjuvant or adjuvant therapy were excluded. The impact of the number of involved lymph nodes on the risk of systemic disease recurrence was assessed using univariate and multivariate analyses. Systemic disease occurred in 40%. The number of involved lymph nodes ranged from 0 to 26 with 55% of patients having at least 1 involved lymph node. The frequency of systemic disease after esophagectomy was 16% for those without nodal involvement and progressively increased to 93% in patients with 8 or more involved lymph nodes. This study shows that the number of involved lymph nodes can be used to predict the likelihood of systemic disease in patients with esophageal cancer. The probability of systemic disease exceeds 50% when 3 or more nodes are involved and approaches 100% when the number of involved nodes is 8 or more. Additional therapy is warranted in these patients with a high probability of systemic disease.

Splenic Marginal Zone Lymphoma (SMZL): Clinical Course after Splenectomy. A Single Institution Experience

SMZL is an indolent B-cell malignancy accounting for 1–2% of chronic lymphoid leukemia found on bone marrow examination and up to 25% of low-grade B-cell neoplasms in splenectomy patients. Aggressive transformation of SMZL rarely occurs. It usually presents as an incidental finding or with symptoms of splenomegaly and anemia. There is still no reliable clinical or biological scoring system for prognostic stratification. We reviewed pathology reports of 41 splenectomized patients at HFHS from 1994 to 2007 and identified 14 patients with splenic marginal zone lymphoma (SMZL). The reasons for splenectomy were symptoms of splenomegaly in all 14 patients, anemia in 13 patients, thrombocytopenia in 12 patients, AIHA in 4 patients, splenic laceration in one patient. We report here the demographics, clinical course and pathology review of these patients. The median age of patients was 77.8 years. There were 7 male and 7 female patients. ECOG performance status was 0–1 in 12(86%), and 2 in 2(14%). Of the 14 patients, 8(57%) were at Ann Arbor stage IV, 1(7%) was at stage III, 4(29%) were at stage II, and 1(7%) at stage I. LDH was above normal in 9(64%) patients B-symptoms were observed in 1(7%).Bone marrow involvement was documented in 8(57%) of the patients. Anemia in 13(93%), thrombocytopenia in 12(86%), AIHA in 4(29%). IPI score was 1–2 in 5(36%), and score 3–4 in 9(64%) of the patients. Median weight of the spleen was 1235 gm. Bone marrow cytogenetics were abnormal in 4(29%) cases. Following splenectomy, cytopenias resolved completely or partially (CR/PR) in 13(93%) patients. Bacterial infections were observed in 4(29%) patients and 2(14%) died of infectious complications. Progressive disease requiring additional systemic therapy was documented in 5(36%) patients. Total of 5(36%) patients died. One secondary to NSLC, 1(7%) of urothelial carcinoma, 1(7%) secondary to hypercalcemia, 2(14%) due to bacterial sepsis. Patients were followed up to 139 months (with median follow-up time of 42 months). The estimated median overall survival (OS) for this group was 116.5 months (9.7 years), the median progression-free survival (PFS) was 91 months (7.6 years). The Kaplan Meier method was used to calculate these estimates. A simple median was calculated for the sample median. In summary, we report the course of 14 patients with SMZL who underwent splenectomy for symptomatic disease. Only 5(36%) required systemic therapy following splenectomy. No death was attributed to progressive SMZL. Overall course was indolent even after splenectomy. Estimated OS was 116.5 months (9.7 years), PFS - 91 month (7.6 years).

Immunosensitization with a Bcl-2 small molecule inhibitor.

Several tumor immunotherapy approaches result in a low percentage of durable responses in selected cancers. We hypothesized that the insensitivity of cancer cells to immunotherapy may be related to an anti-apoptotic cancer cell milieu, which could be pharmacologically reverted through the inhibition of antiapoptotic Bcl-2 family proteins in cancer cells. ABT-737, a small molecule inhibitor of the antiapoptotic proteins Bcl-2, Bcl-w and Bcl-x(L), was tested for the ability to increase antitumor immune responses in two tumor immunotherapy animal models. The addition of systemic therapy with ABT-737 to the immunization of BALB/c mice with tumor antigen peptide-pulsed dendritic cells (DC) resulted in a significant delay in CT26 murine colon carcinoma tumor growth and improvement in survival. However, the addition of ABT-737 to either a vaccine strategy involving priming with TRP-2 melanoma antigen peptide-pulsed DC and boosting with recombinant Listeria monocytogenes expressing the same melanoma antigen, or the adoptive transfer of TCR transgenic cells, did not result in superior antitumor activity against B16 murine melanoma. In vitro studies failed to demonstrate increased cytotoxic lytic activity when testing the combination of ABT-737 with lymphokine activated killer (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand or TNF-alpha against the CT26 and B16 cell lines. In conclusion, the Bcl-2 inhibitor ABT-737 sensitized cancer cells to the antitumor effect of antigen-specific immunotherapy in a vaccine model for the CT26 colon carcinoma in vivo but not in two immunotherapy strategies against B16 melanoma.

Low‐dose etanercept therapy in moderate to severe psoriasis in Korean

Etanercept is a fully humanized soluble tumor necrosis factor (TNF)-alpha receptor that competitively inhibits the interaction of TNF-alpha with cell-surface receptors. It was approved as monotherapy for psoriasis in the USA in 2004, but in Korea, no clinical reports on its use for psoriasis are available. We performed a retrospective analysis of 26 moderate-to-severe psoriasis patients who had been treated with etanercept. Patients received twice-weekly injections of 25 mg etanercept s.c. for at least 4 weeks. When the patients achieved a 50% reduction of the psoriasis area severity index (PASI 50) they received once-weekly injections, then biweekly injections were provided for maintenance. Patients were evaluated biweekly by clinical photographs and PASI scoring. Treatment efficacy was as follows. A PASI 75 was achieved in 14 patients (54%) and the mean number of injections before achieving a PASI 75 was 10 +/- 7.5. Patients whose initial PASI was less than 10 (iPASI < 10) showed an earlier response (2.6 +/- 1.3 weeks) and a higher PASI 75 rate (63%), than with iPASI > or = 10 (6.9 +/- 4.5 weeks, 50%). Eight patients (31%) received additional phototherapy or systemic therapy because of insufficient responses or for faster improvements and they were excluded in the efficacy evaluation. Adverse events were observed in eight patients (31%), but were not serious. This is the first report on the effectiveness of low-dose etanercept regimen on Asian psoriasis patients. Results in this study showed that low-dose etanercept therapy is effective for moderate-to-severe Asian psoriasis patients, and it may be a valuable treatment option even for relatively moderate psoriasis patients not responsive to conventional treatment. In addition, the medical cost was relatively low compared to that of the standard regimen for white patients.

Outcomes of Patients with N3 Neck Nodes Treated with Chemoradiation

To evaluate the outcomes of patients with locally advanced head and neck squamous cell carcinoma with N3 neck nodes treated with definitive chemoradiation. Retrospective review. Thirty-two patients with nonmetastatic locally advanced head and neck squamous cell carcinoma and N3 neck disease treated with concurrent chemoradiation therapy were evaluated. Overall survival, disease- free survival, locoregional control, and distant control were recorded. Median follow-up for surviving patients was 25 (range, 3-93) months. Seventeen of 32 (53%) patients failed, 13 in distant sites only, 2 in the neck only, 1 in the neck and a distant site, and 1 in the neck and primary site. The absolute rates of locoregional control and distant control were 88% and 56%, respectively. Actuarial overall survival and disease-free survival at 2 years were 51% and 29%, respectively. Patients with N3 neck disease treated with chemoradiation experience a very high rate of distant failure. Future studies investigating the role of additional systemic therapy in these patients are warranted.

Neoadjuvant Chemohormonal Therapy in Poor-Prognosis Localized Prostate Cancer

To conduct a trial of neoadjuvant chemohormonal therapy and radical prostatectomy for patients with poor-prognosis localized prostate cancer (prostate-specific antigen [PSA] value 20 ng/mL or greater, Gleason score 8 or higher, and clinical stage T2c or greater), who are at high risk for local and systemic relapse. Complete androgen blockage and four cycles of docetaxel (70 mg/m2) on day 2 and estramustine (280 mg three times daily) on days 1 to 5 every 21 days were given to 22 patients before radical prostatectomy and nerve preservation. Patient characteristics, as median (range), were as follows: age 61 (49 to 70) years, PSA value 21.2 (3.2 to 71.6) ng/mL, and Gleason sum 7 (6 to 9). Clinical stage was T3a-c in 14 patients (64%), T2c in 4 (18%), T2b in 3 (14%), and T1c in 1 (4%). Presurgery characteristics after chemohormonal therapy were as follows: PSA value 0.21 (0.05 to 0.6) ng/mL, clinical stage T1c in 14 patients (63.7%), T2a in 6 (27.3%), and T3a in 2 (9%). The pathologic specimens revealed viable disease in all patients, organ-confined disease in 14 (63.6%), specimen-confined disease in 16 (72.7%), seminal vesicle disease in 9 (40.9%), and lymph node involvement in 4 (18.1%). To date, at a median follow-up of 23.6 (12.1 to 54.7) months, 10 patients (45.4%) relapsed, with PSA doubling time of 1.5 (0.4 to 34.3) months. Of the relapsed patients, 8 (89%) had organ/specimen involvement. The neoadjuvant chemohormonal approach with nerve-preservation surgery is feasible in patients with poor-prognosis localized prostate cancer. It leads to clinical tumor downstaging. The pattern of relapse suggests that local therapy, with radiotherapy for patients with surgical or capsular involvement, and additional systemic therapy should be integrated.

Multimodality management of brain metastases in metastatic melanoma patients

Brain metastases are a frequent complication of advanced melanoma. Neurosurgery (generally followed by radiotherapy) may be useful in managing solitary, superficial brain metastases in good performance status patients, as well as for diagnostic purposes. Since most patients are not felt to be resectable and concurrent extracranial metastases frequently are present, whole-brain radiotherapy (WBRT) has become the de facto treatment standard. WBRT has resulted in disappointing outcomes, resulting in a 3.6–4.1-month median survival. Recent studies have suggested that focal irradiation using linear accelerator-based stereotactic radiosurgery or gamma-knife technologies can result in excellent local control and prolonged survival in some patients. It is possible that more aggressive combined modality treatment strategies, such as addition of systemic therapy, may further improve outcome. Current data suggest that aggressive treatment of patients with up to five brain melanoma brain metastases is capable of producing prolonged survival in many patients, including some long-term complete responses.

The role of postchemotherapy surgery in managing metastatic germ cell tumors

The role of postchemotherapy surgery in managing metastatic germ cell tumors

The Impact on Post-surgical Treatment of Sentinel Lymph Node Biopsy of Internal Mammary Lymph Nodes in Patients with Breast Cancer

BackgroundSince the introduction of the sentinel lymph node (SLN) biopsy in breast cancer patients there is a renewed interest in lymphatic drainage to the internal mammary (IM) chain nodes. We evaluated the frequency of lymphatic drainage to the IM chain, the rate of SLNs that contain metastases and the clinical implications of IM LN metastases.MethodsBetween June 1999 and April 2005 506 consecutive patients underwent SLN biopsy as a staging procedure for clinically T1-2N0 breast cancer. In all patients preoperative lymphoscintigraphy was combined with the intraoperative use of a gammaprobe. In patients with IM SLNs visualized on lymphoscintigraphy, LNs were extirpated through an intercostal parasternal incision.ResultsSLNs were visualized by preoperative lymphoscintigraphy in 99% of all patients (502/506): axillary SLNs in 499 patients (99%), ipsilateral IM LNs in 109 patients (22%). In 85 patients with visualized IM SLNs the IM nodes could be removed (78%). In 20 of the latter 85 patients IM SLNs contained metastases (24%). IM metastases were associated with axillary LN metastases (P < 0.001). In 17 patients IM metastases led to extension of the radiotherapy field, while additional (adjuvant) systemic therapy was given in six patients.ConclusionSLNs in the IM chain are common in breast cancer patients and can be extirpated in the majority of these patients. The proportion of patients in whom radiotherapeutic treatment was adjusted due to IM LN metastases was substantial. We advocate retrieval of IM SLNs when visualized by preoperative lymphoscintigraphy.

Recent developments in the treatment of adult atopic dermatitis

Atopic dermatitis is a common inflammatory skin condition with increasing incidence in recent decades. The mainstay of treatment has been the combination of emollients and topical corticosteroids, with the addition of systemic therapies in severe cases. New drugs such as the topical calcineurin inhibitors have shown promise in treating mild-to-severe atopic dermatitis. Other novel therapies that have been reported in the literature include leukotriene antagonists, monoclonal antibodies such as infliximab, leflunomide, recombinant interferon gamma and intravenous immunoglobulin. This review will focus on the treatment of adult atopic dermatitis.

Synergistic Effect of Interstitial Laser Coagulation and Doxorubicin in a Murine Tumor Recurrence Model of Solitary Colorectal Liver Metastasis

Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model. Single C26 colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium-yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging. Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load. A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.