Tumor Excision Site Research Articles

Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A+CD141+ cDC1 and CD14+ antigen-presenting cell recruitment

BackgroundWe previously reported CpG-B injection at the primary tumor excision site prior to re-excision and sentinel node biopsy to result in immune activation of the sentinel lymph node (SLN), increased...

A New Method for Partial Breast Reconstruction: 3-Year New Zealand Experience.

In New Zealand, oncoplastic surgery is common, but partial breast reconstruction presents challenges for radiation therapy targeting. Tissue rearrangement creates ambiguity when targeting the tumor bed, with resultant overestimation of treatment volumes. Thus, adoption of advanced methods of radiation therapy have been hindered. This pilot study describes use of a novel three-dimensional implant that provides a scaffolding for tissue ingrowth during partial breast reconstruction and delineates the tumor bed more precisely to assist radiation planning and mammographic surveillance. After informed consent, 15 women were implanted with the three-dimensional bioabsorbable implant. The device was sutured to the tumor bed during lumpectomy, and tissue flaps were mobilized and attached to the implant. Visualization of the marker and radiation treatment volumes were recorded and compared. The implant provided volume replacement and helped to maintain breast contour. Cosmetic outcomes were excellent; no device- or radiation-related complications occurred. One patient had a postoperative hematoma that resolved after percutaneous drainage; there were no postoperative infections. Three-year follow-up shows no tumor recurrences and no untoward effects. When compared to conventional radiation targeting, use of the implant showed that a greater than 50 percent reduction in treatment volume was possible in some cases. Three-year mammograms show no significant artifact, normal tissue ingrowth, and minimal fibrosis. This study describes a method of oncoplastic breast reconstruction using an implantable device that marks the site of tumor excision and provides for volume replacement with tissue ingrowth. Patients tolerated it well, and radiation therapy planning, positioning, and treatment were facilitated.

Abstract B138: Single low-dose administration of anti-CTLA-4/tremelimumab at the tumor excision site boosts systemic antitumor immunity in early-stage melanoma patients: Results from a Phase-1 study

Abstract While systemic immune checkpoint blockade is unsurpassed in the induction of clinically effective T cell immunity in advanced-stage melanoma patients, the risk of autoimmune-related side effects precludes its application in earlier stages. In a Phase-1 dose escalation study we have studied the safety, feasibility and immunological effects of intradermal delivery of a single low dose of anti-CTLA-4/tremelimumab at the primary tumor excision site of patients with clinically Stage I-II melanoma. Dose escalation (4x3 cohorts of 2, 5, 10 and 20 mg) has been concluded with one additional patient enrolled in a 20 mg expansion cohort. Breslow thickness ranged from 0.9 to 6 mm (mean 1.98 mm). Examination of the sentinel lymph node (SLN) revealed (micro-)metastases in five of the patients. The tremelimub administration was found to be safe without apparent side effects except for one case of localized vitiligo at the highest (20 mg) dose level. Of note, potent immunological effects were observed in equal measure at all dose levels. In all patients a decrease in systemic rates of activated Tregs (aTregs, defined as CD4+CD25hiFoxP3hi T cells) was observed after 7 days of treatment (p<0.001). In 8/13 patients aTreg rates remained low at 12 weeks whereas in five patients aTreg rates had rebounced to pre-treatment levels by that time. In 11/13 patients the percentage of ICOS expressing CD4+ T cells (a recognized biodynamic marker of CTLA-4 blockade) transiently increased with in 1-3 weeks post-treatment. Specific T cell reactivity against long peptides derived from the melanoma antigens NY-ESO-1 and MART-1 was tested after in vitro re-stimulation in an IFNγ Elispot assay. In 7/13 patients evidence was found of tremelimumab-induced increases in systemic T cell rates, which remained elevated up to 12 weeks post-treatment. Remarkably, 5/13 patients showed pre-existent NY-ESO-1 reactivity, which in all cases had decreased by day 7, and in 3/5 patients had increased over baseline levels by day 21. T cell reactivity to either NY-ESO-1 or MART-1 was observed in 4/4 tested SLN. Of note, both NY-ESO-1 and MART-1 reactive T cells were detected in the SLN of the patient experiencing an isolated incidence of vitiligo after receiving 20 mg tremelimumab. In conclusion, local administration of a single low dose of anti-CTLA-4/tremelimumab has proven safe and effective in terms of attenuating aTreg levels in peripheral blood and boosting systemic antitumor immunity. As such it may offer an attractive, and up to now sorely lacking, adjuvant treatment option for early-stage melanoma patients at risk for tumor recurrence. Citation Format: Anita G.M. Stam, Kim M. van Pul, Bas D. Koster, Dafni Chondronasiou, Sinéad M. Lougheed, M. Petrousjka van den Tol, Karin Jooss, Ronald J.C.L.M. Vuylsteke, Alfons J.M. van den Eertwegh, Tanja D. de Gruijl. Single low-dose administration of anti-CTLA-4/tremelimumab at the tumor excision site boosts systemic antitumor immunity in early-stage melanoma patients: Results from a Phase-1 study. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B138.

Pulsed-dose-rate peri-operative brachytherapy as an interstitial boost in organ-sparing treatment of breast cancer.

PurposeTo evaluate peri-operative multicatheter interstitial pulsed-dose-rate brachytherapy (PDR-BT) with an intra-operative catheter placement to boost the tumor excision site in breast cancer patients treated conservatively.Material and methodsBetween May 2002 and October 2008, 96 consecutive T1-3N0-2M0 breast cancer patients underwent breast-conserving therapy (BCT) including peri-operative PDR-BT boost, followed by whole breast external beam radiotherapy (WBRT). The BT dose of 15 Gy (1 Gy/pulse/h) was given on the following day after surgery.ResultsNo increased bleeding or delayed wound healing related to the implants were observed. The only side effects included one case of temporary peri-operative breast infection and 3 cases of fat necrosis, both early and late. In 11 patients (11.4%), subsequent WBRT was omitted owing to the final pathology findings. These included eight patients who underwent mastectomy due to multiple adverse prognostic pathological features, one case of lobular carcinoma in situ, and two cases with no malignant tumor. With a median follow-up of 12 years (range: 7-14 years), among 85 patients who completed BCT, there was one ipsilateral breast tumor and one locoregional nodal recurrence. Six patients developed distant metastases and one was diagnosed with angiosarcoma within irradiated breast. The actuarial 5- and 10-year disease free survival was 90% (95% CI: 84-96%) and 87% (95% CI: 80-94%), respectively, for the patients with invasive breast cancer, and 91% (95% CI: 84-97%) and 89% (95% CI: 82-96%), respectively, for patients who completed BCT. Good cosmetic outcome by self-assessment was achieved in 58 out of 64 (91%) evaluable patients.ConclusionsPeri-operative PDR-BT boost with intra-operative tube placement followed by EBRT is feasible and devoid of considerable toxicity, and provides excellent long-term local control. However, this strategy necessitates careful patient selection and histological confirmation of primary diagnosis.

Mammographic imaging after partial breast reconstruction: Impact of a bioabsorbable breast implant.

111 Background: Marking the site of the excised tumor bed during partial mastectomy is critical for radiation targeting and surveillance for breast cancer recurrence. However, delineating the lumpectomy cavity margins is challenging, and dense fibrosis and scarring often present obstacles when reviewing post-operative mammograms for signs of early recurrence. To determine whether implantation of a "mini" breast implant used for partial breast reconstruction adversely affected post-operative breast imaging, we reviewed clinical imaging of 100 patients that had been implanted with a new bioabsorbable breast implant over a three year period. Methods: Following informed consent, 110 patients were implanted at the time of partial mastectomy with a bioabsorbable implant with a primary purpose of marking the surgical site of tumor excision for radiotherapy. In each case, the surgeon sutured the implant into the cavity at the location believed to be at greatest risk for recurrence. Implants were used for partial breast reconstruction, a guide for radiation treatment planning and routine mammographic follow-up. Mammograms were reviewed for implant visibility, presence of artifacts and other diagnostic criteria. Results: In all cases the implant was rated as easily visible on mammography and CT without appreciable artifact or interference with diagnostic capabilities. In addition, there was notably less dense fibrotic tissue visualized on mammographic imaging at the tumor excision site containing the implant. In some cases, the marker clips coalesced in the center of the surgical cavity. The marker was also seen on US and MRI during routine follow-up. Conclusions: Mammographic imaging in patients implanted with this new device was not adversely affected by its presence. The implant visually assisted with verification of the excised tumor bed without introducing any artifact or diagnostic interference and there was notable in-growth of normal breast tissue clearly seen on mammography. In this group of patients there were no abnormal calcifications in or around the implant and there were no recurrent cancers detected within this 36 month period.

A new method for partial breast reconstruction: 3-year New Zealand experience.

89 Background: Most women in New Zealand undergo partial mastectomy (PM) and 6 weeks of whole breast irradiation for early breast cancer. Oncoplastic surgery (OPS) is common, however, reconstruction of the breast during partial mastectomy presents challenges for radiation targeting since tissues have been extensively rearranged. Further complicating matters, the seroma cavity is often absent, and many patients travel to different cities for radiation without much communication between the surgeon and radiation oncologist prior to treatment. Throughout the country there is interest in promoting hypofractionated or accelerated radiotherapy, however, these techniques cannot be popularized without accurate targeting to minimize complications. In this series of patients we studied a new method of breast reconstruction using a bioabsorbable implant that serves as a surgical site marker as well. Methods: Following informed consent, 15 women were studied in a prospective manner. The bioabsorbable implant was sutured into the tumor resection site, and tissue flaps were directly attached. Radiation treatment protocols followed ASTRO guidelines. Results: The implant provided volume replacement and acted as a scaffolding for the breast tissue flaps providing local reconstruction. Cosmetic outcomes were excellent in all patients, no device related or radiation complications occurred. One patient had a post-operative hematoma that resolved without intervention, there were no post-operative infections. 3 year follow up shows no tumor recurrences, and no untoward effects. When compared to conventional radiation targeting, use of the implant showed a > 50% reduction in treatment volume is possible. 3 year mammograms show normal regrowth of tissue without artifact and with minimal fibrosis. Conclusions: Three year follow-up shows this "mini" breast implant assists with oncoplastic breast reconstruction, while at the same time clearly marks the surgical site of tumor excision. Patients tolerated it well, and radiotherapy planning, positioning and treatment were all facilitated by the implant. Excellent patient outcomes in this pilot study have resulted in a national evaluation of this method in the public healthcare sector.

Abstract 5618: Arming the melanoma sentinel lymph node against tumor spread: The effects of local administration of combined low-dose CpG-B PF-3512676 and GM-CSF

Abstract The sentinel lymph node (SLN) procedure has proven a useful prognostic tool for the assessment of melanoma relapse and mortality risk, but is also of great value for the assessment of immunological interventions. Since early melanoma development is accompanied by a suppressed immune state of the SLN, there is a strong rationale for therapeutic immune modulation of the SLN in order to strengthen local as well as systemic cell-mediated anti-tumor immunity. Previous Phase II studies showed promising immunostimulatory effects on the melanoma SLN of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF) and the CpG-B oligodeoxynucleotide PF-3512676. The present 3-arm Phase II study was designed to determine the effects of combined low-dose GM-CSF+CpG-B administration. Stage I-III melanoma patients (n=28) were randomized to receive i.d. injections around the primary tumor excision site of saline, CpG-B alone (1 mg), or CpG-B combined with GM-CSF (100 μg), 7 and 2 days prior to surgical excision of the SLN. Flowcytometric DC analyses revealed significantly increased maturation of all identifiable cDC and pDC SLN subsets upon administration of CpG-B with or without GM-CSF, but remarkably, the combination resulted in significantly higher levels of co-stimulatory molecules on both cDC and pDC. In addition, a significant CpG-related increase in frequencies of CD1a−CD11chiCD14+/− cDC subsets was observed in the SLN, possibly resulting from DC and/or monocyte mobilisation from blood. Indeed, increased activation of pro-inflammatory 6-sulfo LacNac+slanDC, monocytes, and pDC was observed in peripheral blood upon administration of CpG-B alone, and additionally of CD1c+ cDC when combined with GM-CSF. In the case of slanDC this activation was accompanied by significantly reduced frequencies. Peripheral blood rates of CD14+DRlo myeloid suppressors remained unchanged after saline or combined CpG and GM-CSF administration, but significantly decreased after administration of CpG-B alone. T cell analyses revealed a CpG-related increase in CTLA-4 and FoxP3 levels on Tregs in SLN, without changes in their actual rates. Nevertheless, higher intracellular Th1 cytokine levels were detected in ex vivo expanded T cells of CpG-administered patients than of patients receiving saline or CpG-B+GM-CSF. In keeping with this, also higher frequencies were found in SLN of MAA-specific CD8+ T cells in low dose CpG-B administered patients (n=4) than in saline controls (n=5), as determined by tetramer binding and cytokine release. We conclude that the imunomodulatory effects observed in melanoma SLN upon local administration of combined low-dose GM-CSF and CpG-B are mostly attributable to CpG-B and that they are consistent with the induction of protective cell-mediated anti-tumor immunity. 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 5618.

Adjuvant Immunotherapy of Feline Fibrosarcoma with Recombinant Feline Interferon‐ω

Background: Recombinant feline interferon‐ω (rFeIFN‐ω) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Hypothesis: Treatment with rFeIFN‐ω in cats with fibrosarcoma is safe and feasible. Animals: Twenty domestic cats. Methods: In an open‐labeled uncontrolled clinical trial 12 injections of 1 × 106 U/kg rFeIFN‐ω were administered over a 5‐week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN‐ω. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN‐ω and recombinant feline interferon‐γ was performed to assess the biological effect of rFeIFN‐ω. Results: Changes in blood cell count, increases in serum aspartate‐amino‐transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P= .025), neutropenia (P= .021), and weight loss (P < .001) were statistically correlated with rFeIFN‐ω‐treatment (analysis of parameters before treatment and after 3 injections of rFeIFN‐ω). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P= .026) in response to in vitro incubation with rFeIFN‐ω, whereas expression of MHC class II molecules was not affected significantly. Conclusions and Clinical Importance: RFeIFN‐ω for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo‐controlled trial.

Adjuvant Immunotherapy of Feline Fibrosarcoma with Recombinant Feline Interferon-ω

Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. Twenty domestic cats. In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.

Cytokine‐containing gelfoam implants at a postsurgical tumor excision site to stimulate local immune reactivity

We previously demonstrated increased numbers of CD34(+) progenitor cells in the peripheral blood of tumor bearers. Also demonstrated was the feasibility of chemoattracting these cells by sponge implants containing VEGF. The present study used a murine Lewis lung carcinoma (LLC) model to test if CD34(+) cells that are chemoattracted to a tumor excision site can be differentiated in situ into dendritic cells and whether this leads to increased local immune reactivity. After surgically excising established LLC tumors, mice received at the excision site gelatin sponge implants containing VEGF to chemoattract CD34(+) cells, and/or GM-CSF plus SCF to induce CD34(+) cell differentiation into dendritic cells. In some studies, lysates of GFP-transfected LLC cells (LLC(GFP)) were also included in the implants as a source of tumor antigen. After 2 weeks, implants and local lymph nodes were removed and analyzed. Implants containing VEGF, GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher proportion of CD34(+) cells compared to control implants. However, the number of dendritic cells was higher in implants containing GM-CSF/SCF or VEGF/GM-CSF/SCF than those containing either VEGF or diluent. Regional lymph node from mice containing GM-CSF/SCF or VEGF/GM-CSF/SCF implants showed increased dendritic cell levels. However, when lysates from LLC(GFP) were added to the implants, the highest proportion of dendritic cells associated with GFP was in lymph nodes of mice containing GM-CSF/SCF implants. Lymph node cells from mice with GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher level of proliferation and IFN-gamma secretion in response to in vitro LLC lysate challenge, with the greatest response being from lymph node cells of mice with GM-CSF/SCF implants. These results suggest the feasibility of using GM-CSF/SCF-containing implants to increase dendritic cell levels, uptake of tumor antigens, trafficking to lymph nodes and stimulation of immune reactivity at tumor excision sites with residual tumor.

Conservation therapy in T1-T2 breast cancer: past, current issues, and future challenges and opportunities.

To assess the significance of patient age, race, tumor-related prognostic parameters, status of surgical excision margins, and irradiation boost on incidence of ipsilateral breast relapse, and to review current issues in the management of T1-T2 breast cancer patients with conservation therapy. Records of 1037 patients with histologically confirmed stage T1 and 308 patients with T2 carcinoma of the breast treated with breast conservation therapy from January 1970 through December 1997 were prospectively registered and evaluated. The mean follow-up for surviving patients was 6.6 years (range, 4-30 years), with a minimum follow up of 4 years for all patients. There were 78 ipsilateral breast relapses (IBRs); the actuarial 10-year incidence of IBR was 7% for T1 and 11% for T2 tumors. In patients 40 years of age or younger, four of 24 (17%) with extensive intraductal component developed an ipsilateral breast relapse, compared with six of 80 (8%) without extensive intraductal component, in contrast to eight of 159 (5%) and 33 of 776 (4%) in postmenopausal patients with or without extensive intraductal component, respectively. In patients with T2 tumors, two of eight (25%) women 40 years or younger with extensive intraductal component, and seven of 50 (14%) without extensive intraductal component developed ipsilateral breast relapse. The corresponding values for the patients older than 40 years were five of 48 (10%) and 13 of 202 (6%), respectively. The incidences of ipsilateral breast relapses, correlated with status of surgical margins after re-excision in T1 tumors, were one of 30 (3.3%) for positive, no relapses in 40 patients with close margins, 16 of 438 (3.6%) for negative, and 18 of 196 (9%) for undetermined margins. In the patients with T2 tumors, ipsilateral breast relapses occurred in two of 16 patients (12.5%) with positive margins, one of 16 (6%) with close, seven of 105 (6.6%)with negative, and four of 68 (5.9%) with undetermined margins (differences not statistically significant). In patients with T1 tumors, negative margins, the 10-year relapse rate was the same (8%) in 559 to whom a boost was administered and in 66 without a boost. In patients with positive margins, the relapse rate was 4% in 215 receiving a boost (18-20 Gy) and 33% (two of six) without a boost. In patients with T2 tumors and negative margins, the rate of ipsilateral breast relapses in 16 patients to whom no boost was given was 12%, as opposed to 10% in 143 patients who received a boost. However, with T2 tumors and close or positive margins, the IBR rate at 10 years was 12% in 81 given a boost, in contrast to 40% (2 of 5) without a boost. In T1 tumors, the breast failure rate was two of 53 (3.7%) in women < or = 40 years receiving chemotherapy and eight of 51 (15.6%) without chemotherapy. For T2 tumors, the corresponding values were seven of 39 (17%) and two of 19 (10.5%), respectively. In women 40 years or younger with T1 tumors receiving hormones or not, the ipsilateral breast relapse rate was two of 19 (10.5%) and eight of 85 (9.4%), respectively; in the older than 40 years group, the corresponding values were six of 377 (1.6%) and 35 of 558 (6.2%). In the patients with T2 tumors, ipsilateral breast relapse rates were not statistically different in the various groups. On multivariate analysis, only age and adjuvant therapy were significant factors predictive of ipsilateral breast relapse. Surgical excision margins status following adequate doses of radiation therapy was not a predictor of ipsilateral breast relapse. In patients younger than 40 years of age with extensive intraductal component, a somewhat higher breast relapse rate was noted but not enough to preclude breast conservation therapy. A boost of irradiation did not have a significant impact in the incidence of ipsilateral breast relapse in patients with negative margins, but it was of benefit to those with close or positive margins. Close attention to surgical margin status and delivery of higher doses of irradiation to the tumor excision site in patients with close or positive surgical margins will decrease the probability of breast relapses.

Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of tumor excision as the first step of an immunotherapeutic approach to target residual tumor cells.

The authors previously showed that C34+ progenitor cells are mobilized into the peripheral blood in tumor bearers. The current study used a murine Lewis lung carcinoma (LLC) model to examine if the CD34+ cells can be chemoattracted to a tumor excision site as the first step to inducing differentiation of the attracted CD34+ cells into immune stimulatory dendritic cells (DC). Upon tumor excision, gelatin sponges were implanted into the surgical site and infused with phosphate-buffered saline or vascular endothelial cell growth factor (VEGF). The implants were removed after 4, 7, 14, and 21 days and analyzed for their cellular content. The incorporation of VEGF into implants increased the accumulation of CD34+ cells early after implantation. By day 21, the CD34+ cell content declined. However, the numbers of DCs became increased in the VEGF-containing sponges and this persisted throughout the 3-week duration of the study. The VEGF-containing implants contained a lower percentage of CD11b+ myeloid cells for the first 2 weeks after implantation as compared with the control implants. By 21 days, myeloid cell numbers declined in the control and VEGF implants. Since endothelial cell precursors have a common precursor with myeloid progenitor cells, the implants were also examined for their endothelial cell content. With increasing time after implantation, the number of endothelial cells and formation of vessel-like structures became greater in the VEGF-containing implant as compared with the control implants. These results show the feasibility of using VEGF-containing sponges to attract DC precursors and to increase the number of DCs at the tumor excision site.

Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: A nonrandomized comparison

The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes

Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous 'activated' lymphocytes expressing in vitro tumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2--based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines.

Preoperative planning of breast implants using the Breast Implant Planning Device (BIPD)

Interstitial implantation of the tumor excision site is an important component of the treatment program of breast-conserving surgery and irradiation. The currently accepted method of designing and performing the implant in the operating room does not assure adequate coverage of the volume of tissue at risk, i.e., the tissue immediately adjacent to the walls of the original tumor excision cavity. This communication describes a technique of preoperative implant planning that consistently and reliably ensures adequate coverage of the volume of tissue at risk. An integral part of this technique is the use of a new device called the Breast Implant Planning Device. This device is a modification of previously described implant template devices.