Tumor Bed In Patients Research Articles

5-Year Results from a Prospective Phase II Trial of Ten-Fractions Hypofractionated Radiotherapy in Locally Advanced Breast Cancer

There is a growing interest for adjuvant loco-regional hypofractionated radiotherapy (Hypo-RT) regimens in patients (pts) undergoing surgery for locally advanced breast cancer (LABC). We report the 5-year results of a phase II study on Hypo-RT targeting the primary and regional lymph nodes in ten fractions (fxs). A schedule of 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes was used; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE 4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up (fup) examination (1, 3, 6 months and then yearly). Late toxicity was assessed starting from 3 months after the end of Hypo-RT and loco-regional toxicity was prospectively collected. Cancer related endpoints in terms of loco-regional (LR) recurrence, distant metastasis, specific disease- free survival and overall survival (OS) were evaluated from the date of RT start to the diagnosis of local relapse/distant metastases or the last fup respectively. From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) were accrued. One patient was lost to fup immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (27.5%) or adjuvant (57%) chemotherapy and 15.5% exclusive hormone therapy as well. Trastuzumab was administered concomitant to RT in HER2 positive pts (25%). All pts completed treatment as planned. No grade 2+ acute toxicity was recorded. At the median fup of 63 months (range: 25-92 mths), the cumulative incidence of any grade locoregional late toxicity estimated with the Kaplan-Meier method is 43.4% (95% CI) (30.0% and 46.1% for patients undergone mastectomy and lumpectomy, respectively). Peak 2 events have been observed for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%) and lymphoedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. Of all eligible patients (N = 51), patient reported cosmetic outcome was excellent, good, fair and poor in 51.7%, 22.4%, 10.3% and 3.4%, respectively. No late lung toxicity was observed. The actuarial LR control rate at 5 years is 98%; for distant metastasis-free survival, specific disease-free survival and OS rates are 89.2%, 80.8% and 93.7% respectively. Our results support the activity of a 10-fxs Hypo-RT schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.

Feasibility of accelerated image-guided high-dose-rate interstitial brachytherapy with inverse planning simulated annealing (IPSA-HDRBT) for post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue

Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence. Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4-8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively. IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned.

Feasibility of interaortocaval clamping for renal artery during robot-assisted right partial nephrectomy: A propensity score-matching analysis.

To evaluate the impact of the interaortocaval clamping technique for the right renal artery on perioperative outcomes of patients who underwent robot-assisted partial nephrectomy (RAPN). This study included 111 consecutive patients with right renal masses undergoing RAPN via the transperitoneal approach. In this series, standard and interaortocaval clamping techniques were defined as those for the right renal artery at the renal hilus and interaortocaval space, respectively. Based on the 3D images reconstructed from CT, interaortocaval clamping was preoperatively selected for patients in whom standard clamping of the main renal artery at the right hilum was judged to be technically difficult due to complicated vascular distribution, such as multiple branches of right renal arteries and veins and/or intertwining of these vessels. Of 111 patients, 95 and 16 were classified into the standard and interaortocaval clamping groups, respectively, and interaortocaval clamping was uneventfully performed as planned in all 16. After adjusting patient variables by 1:3 propensity score-matching, 33 and 11 patients were included in the respective groups, and there were no significant differences in major clinical characteristics between them, while the incidences of multiple branches of right renal vessels as well as their intertwining beside the right renal hilus were significantly higher in the interaortocaval clamping group. However, no significant difference was noted in any of the perioperative outcomes, including operative time or intraoperative blood loss, between the two groups. The interaortocaval clamping technique during RAPN is a feasible procedure with acceptable perioperative outcomes compared with standard hilar clamping, making it possible to more accurately resect renal tumors under clear visualization without unnecessary arterial bleeding from the tumor bed in patients with complex vascular distribution at the right renal hilus; however, special attention should be paid to the considerable individual variability of the interaortocaval anatomy.

Ten Fraction Adjuvant Hypofractionated Radiotherapy in Node Positive Breast Cancer: 3 Year-Follow-Up of a Phase II Toxicity Study

Post-operative loco-regional (LR) hypofractionated radiotherapy (Hypo-RT) is an attractive approach in locally advanced breast cancer (LABC). The aim of this study is to report the preliminary results of a 10 fraction hypofractionated schedule in patients (pts) with resected LABC.The present is a single arm phase II study assessing toxicity outcomes after 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE v4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up examination (1, 3, 6 months and then yearly).From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) entered the study. One patient refused follow up immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (41%) or adjuvant (59%) chemotherapy. Trastuzumab was administered concomitant with RT in all HER2 positive pts (25%). RT was delivered initially with a conformal 3D-CRT (32.8%) and then with an optimized IMRT (67.2%) technique to improve the dose distribution. A deep inspiration breath hold technique was used in compliant left-sided LABC pts (48.4%). All ptscompleted treatment as planned. At a median follow up of 42.3 months (IQR 31.4-57.2 mths), no locoregional failures have been observed. Peak acute toxicity was as follows: grade 0, 30 pts (51.7%); grade 1, 25 pts (43.1%); grade 2, 3 pts (5.2%); no grade > 2 toxicity was recorded. Regarding late toxicity, peak 2 events were found for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%); lymphedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. No other grade 2+ events were reported. Of eligible patients (N = 51) patient-reported cosmetic outcome was excellent, good, fair and poor in 59%, 23.5%, 11.7% and 5.8%, respectively.These preliminary data support the feasibility and tolerability of our 10-fraction fractionation schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.

Abstract 4554: Functionally distinct T cell subsets contribute to ImmTAC-mediated anti-tumor response

Abstract Introduction: Bispecific T cell engagers hold promise for effective cancer treatment. The anti-tumor activity of these therapeutics molecules predominantly relies on their capacity to induce direct killing of tumor cells by engaging the cytotoxic machinery of polyclonal CD8+ T cells. However, the impact of additional functionally different T cell populations that can be engaged alongside CD8+ T cells remains unclear. ImmTAC molecules are a novel class of bispecific fusion proteins that use an affinity-enhanced monoclonal TCR to target tumor antigen-derived peptides presented by HLA, and an anti-CD3 monomeric antibody to engage T cells. Tebentafusp, our lead clinical candidate, targets a gp100-derived peptide and is under clinical investigation in metastatic melanoma. Preliminary data revealed T cell activation, trafficking and infiltration into the tumor bed in patients responding to treatment. Importantly not only CD8+ T cells, but also different subsets of CD4+ T cells appeared to be activated, mobilized and redirected to the tumor site following tebentafusp treatment, suggesting a potential contribution of these T cell subsets to the anti-tumor response. The aim of this study was to investigate in vitro the functional capacity of different T cell populations, besides CD8+ T cells, following ImmTAC-mediated redirection toward cancer cells. Methods: Th1, Th2, Th17 CD4+ T cells, γδ T cells and Mucosal-Associated Invariant T cells (MAIT) were isolated from healthy volunteers and their functional response following exposure to ImmTAC in the presence of target cells was analysed. Results: In addition to CD8+ T cells, other T cell populations, were activated in vitro by ImmTAC and elicited a range of effector functions that may differentially contribute to anti-tumor responses. For example, we found that γδ T cells were able to mount rapid and potent cytokine and cytotoxic responses against cancer cells upon redirection with ImmTAC. The mechanisms that underpin our in vitro observations and the potential correlations in patients treated with tebentafusp are under investigation. Conclusions: Multiple T cells populations display functionally distinct responses following ImmTAC-mediated redirection. These results will add valuable insight to our understanding of bispecific T cell engager mechanism of action. In addition, they will help guide rationale for improving the design of these therapeutic molecules and select appropriate combination strategies. Citation Format: Adel Benlahrech, David K. Cole, Christopher J. Holland, Rupert Kenefeck, Rahul C. Khanolkar, Cheryl McAlpine, Sion Lewis, Angela Valerio-Fernandes, Mariantonella Vardeu, David Berman, Marco Lepore. Functionally distinct T cell subsets contribute to ImmTAC-mediated anti-tumor response [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4554.

The diagnostic accuracy of 12-point core biopsy of a tumor bed compared to the study of surgically obtained breast tissue in patients with locally advanced triple-negative or HER2-positive breast cancer after neoadjuvant systemic and targeted therapy.

e12097 Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy implicate surgical treatment in specific patient groups can be avoided. The core biopsy of the tumor bed and some diagnostic approaches (breast ultrasound, mammography, SPECT/CT) allow for precise evaluation of the treatment efficacy. Methods: This research started in our department in 2018, we picked two groups of 15 patients each treated for locally advanced TNBC or grade cT1-4N1-3M0 HER2-positive breast cancer: HER2+/ER+ or HER2+/ER- breast cancer. The TNBC group received 6 cycles of NACT of paclitaxel combined with doxorubicin and carboplatin AUC5. The HER2+ group received 4 cycles of АС polychemotherapy followed by 4 cycles of monochemotherapy with the docetaxel and 3-weekly trastuzumab. The HER2+ group is receiving adjuvant trastuzumab for up to one year, where ER-positive patients are also given hormone therapy with tamoxifen or aromatase inhibitors. The response to neoadjuvant treatment was assessed in all patients using standard two-dimensional mammography, ultrasound elastography, and SPECT-CT. The 12-point core biopsy of a tumor bed was performed in the operating room setting by previously marked tumor projections. Then, all patients underwent either breast-conserving surgery or mastectomy with immediate reconstruction with expander/implant. Results: After neoadjuvant therapy, in a group of 15 patients with TNBC in surgically obtained material, the pathologic complete response (pCR) was observed in 8 patients (53.33%), whereas residual disease was found in 7 (46.67%) patients. The core biopsy results showed no tumor cells in 10 (66.67%) patients, and were detected in 5 (33.33%) patients (p = 0.0011), the accuracy of the method in this group was 80%. The overall response rate in the group of 15 patients with HER2-positive breast cancer was 8 (53.33%) patients with residual disease and 7 (46.67%) patients with pCR. According to core biopsy, tumor cells were present in 3 (20%) patients and were absent in 12 (80%) patients (p = 0.0787). Conclusions: Avoiding surgical treatment through not less than 12-point core biopsy of a tumor bed in patients with complete regression after neoadjuvant therapy is a new trend in the treatment of breast cancer. Any new approach in this sphere requires a long-term elaboration, compliance with the safety principles, rethinking standard procedures and following-up patients.

P05.75 Surgery followed by fractionated radiosurgery on the tumor bed in patients with single large brain metastases from solid tumor: preliminary results of a phase II study

P05.75 Surgery followed by fractionated radiosurgery on the tumor bed in patients with single large brain metastases from solid tumor: preliminary results of a phase II study

Acute Toxicity Effect of Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Boost of the Tumor Bed in Patients With Breast-Conserving Treatment

Acute Toxicity Effect of Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Boost of the Tumor Bed in Patients With Breast-Conserving Treatment

Prognostic factors in patients with thoracic esophageal carcinoma staged pT1-4aN0M0 undergone esophagectomy with three-field lymphadenectomy.

To analyze prognostic factors in patients with thoracic esophageal carcinoma staged pT1-4aN0M0 and undergone esophagectomy with 3-field lymphadenectomy and to evaluate the effect of postoperative radiotherapy. From January 1993 to March 2007, 770 patients with stage pT1-4aN0M0 underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China were enrolled for analysis. The study consisted of 770 patients with stage pT1-4aN0M0 who underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China. A total of 687 had received surgery only, and 83 patients had undergone surgery followed by postoperative radiotherapy. Radiation dose was 50 Gy in 25 fractions. The overall survival rates at 1, 3, 5, and 10 years were 92.9%, 80.8%, 71.7% and 57.4%, respectively. Univariate analysis showed that age and T staging were two independent factors on prognoses. Five-year survival in cases younger and older than 60 were 76.5% vs. 63.3% (P=0.001), while those of pT1, pT2, pT3 and pT4a were 83.8%, 78.8%, 67.8% and 54.1%, respectively (P=0.000). Five-year survival in group of simple surgery was 71.3%, compared with 74.5% in group of surgery plus postoperative radiotherapy (P=0.763), while stratified analysis indicated that postoperative radiotherapy was able to boost the survival of patients in pT4a which were 72.4% vs. 33.8% (P=0.036) and to lower relapse rate of tumor bed in patients with pT4a (P=0.005). Multivariate analysis showed that age and T staging were two independent factors on prognoses. Patients with high T staging and at an age more than 60 turned out bad prognoses, neither could postoperative radiotherapy improve their survival.

Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity

Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n=3) and MR perfusion (n=7) and PET (n=4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60)=11.2; p<0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care.

Accelerated Intensity-Modulated Radiotherapy to Breast in Prone Position: Dosimetric Results

To report the physics and dosimetry results of a trial of accelerated intensity-modulated radiotherapy to the whole breast with a concomitant boost to the tumor bed in patients treated in the prone position. Patients underwent computed tomography planning and treatment in the prone position on a dedicated treatment platform. The platform has an open aperture on the side to allow for the index breast to fall away from the chest wall. Noncontrast computed tomography images were acquired at 2.5- or 3.75-mm-thick intervals, from the level of the mandible to below the diaphragm. A dose of 40.5 Gy was delivered to the entire breast at 2.7-Gy fractions in 15 fractions. An additional dose of 0.5 Gy was delivered as a concomitant boost to the lumpectomy site, with a 1-cm margin, using inverse planning, for a total dose of 48 Gy in 15 fractions. No more than 10% of the heart and lung volume was allowed to receive >18 and >20 Gy, respectively. Between September 2003 and August 2005, 91 patients were enrolled in the study. The median volume of heart that received > or =18 Gy was 0.5%, with a maximal value of 4.7%. The median volume of ipsilateral lung that received > or =20 Gy was 0.8%, with a maximum of 7.2%. This technique for whole breast radiotherapy is feasible and enables an accelerated regimen in the prone position while sparing the lung and heart.

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.

Early postoperative paclitaxel followed by paclitaxel and cisplatin concurrent with radiation therapy (RT) (phase II trial RTOG H-0024) is well tolerated for patients with resected, high-risk squamous carcinoma of the head and neck (HNSCC)

To test a regimen of early post-operative chemotherapy followed by concurrent chemoradiation. This approach was designed to combat the regenerative response of sub-clinical tumor clones persisting in a growth factor-rich postoperative tumor bed in patients receiving post-operative (post-op) RT for high-risk HNSCC.

Early postoperative paclitaxel followed by paclitaxel and cisplatin concurrent with radiation therapy (RT) (phase II trial RTOG H-0024) is well tolerated for patients with resected, high-risk squamous carcinoma of the head and neck (HNSCC)

To test a regimen of early post-operative chemotherapy followed by concurrent chemoradiation. This approach was designed to combat the regenerative response of sub-clinical tumor clones persisting in a growth factor-rich postoperative tumor bed in patients receiving post-operative (post-op) RT for high-risk HNSCC. Eligible patients had grossly resected stage III/IV HNSCC with positive margins, extra-nodal extension, or multiple metastatic lymph nodes. Conformal RT (58–64 Gy/5.5-6W) started 28–35d post-op. Paclitaxel (80 mg/m2) was given once weekly during post-op weeks 2, 3, and 4 before beginning RT (induction). Paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) were given once weekly during the last 3 weeks of RT (concurrent). The NCI Common Toxicity Criteria version 2.0 was used to score acute effects, and the RTOG/EORTC scale was used to score late effects. The primary endpoint was compliance (using RTOG 9501 as a reference), defined as delivering at least 90% of protocol RT dose, 3 doses of pre-radiation chemotherapy starting no later than post-operative day 18, and at least 2 of 3 doses of concurrent chemotherapy. The secondary endpoint is the rate of grade 5 and acute non-hematologic grade 4 toxicities. Seventy patients entered between 3/5/2001 and 5/23/2003; 64 are analyzable. Forty-five (70%) had nodal risk, and 19 (30%) had positive margins. Primary tumor sites included: oropharynx 21 (33%), oral cavity 23 (36%), larynx 15 (23%), and hypopharynx 5 (8%). Primary tumor T-stages were: T4: 26 (41%), T3: 11 (17%), T2: 18 (28%), and T1: 5 (8%), Tis 2 (3%), and unknown 2 (3%). Fifty-five (86%) had N2, 6 (9%) had N1, and 2 (3%) had N0 disease; the nodal status of one was unknown. The estimated compliance rate is 71.9% [95% confidence interval (59.2%, 82.4%)]. There was one treatment-related death from myocardial ischemia. Six additional patients experienced grade 4 non-hematologic toxicities. There was one fistula, and no serious wound infections were reported. Early post-op induction chemotherapy followed by concurrent chemoradiation therapy is safe and well tolerated, and met compliance goals according to protocol definition. Outcome will be analyzed once each patient has been potentially followed for two years to determine if this new approach has promise to address the above biologic risk factors for recurrence

Assessment of Response to Neoadjuvant Chemotherapy in Breast Cancer: Imaging Considerations

This article reviews current imaging techniques for assessing response to neoadjuvant chemotherapy in women with breast cancer. The rationale for the use of neoadjuvant chemotherapy is presented along with the need to accurately monitor response to therapy. Clinical examination, mammography, sonography, magnetic resonance imaging (MRI), sestamibi imaging, and positron emission tomography (PET) are assessed as techniques for monitoring response to preoperative chemotherapy. Also, placement of metal markers into the tumor bed in patients who demonstrate a favorable response to neoadjuvant chemotherapy is discussed.

A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma.

We studied the function of antitumor T and natural killer T (NKT) cells from the blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive myeloma, or progressive multiple myeloma. We show that antitumor killer T cells can be detected in patients with both progressive or nonprogressive myeloma. Vα24+Vβ11+ invariant NKT cells are detectable in the blood and tumor bed of all cohorts. However, freshly isolated NKT cells from both the blood and tumor bed of patients with progressive disease, but not nonprogressive myeloma or premalignant gammopathy, have a marked deficiency of ligand-dependent interferon-γ production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, α-galactosylceramide (α-GalCer). Fresh myeloma cells express CD1d, and can be efficiently killed by autologous NKT cells. We hypothesize that presentation of tumor derived glycolipids by myeloma cells leads to NKT dysfunction in vivo. These data demonstrate that clinical progression in patients with monoclonal gammopathies is associated with an acquired but potentially reversible defect in NKT cell function and support the possibility that these innate lymphocytes play a role in controlling the malignant growth of this incurable B cell tumor in patients.

1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas

Purpose : To analyze prospectively the prognostic significance of 1H magnetic resonance spectroscopy (MRS) in vivo recorded from the tumor bed of patients after surgery for malignant glioma. Methods and Materials : Fifty-one patients aged 20–68 years were examined using a MRI/MRS system (Elscint 2T Prestige). Of the 51 patients, 33 had Grade 3 gliomas and 18 had glioblastomas. MRI-localized 1HMR spectra were acquired using a single-voxel, double-spin-echo sequence. Relative intensities of the signals (choline, creatine [Cr] N-acetyl aspartate [NAA], myo-inositol, lactate, and lipids) were obtained by numeric integration of fitted signals. Two voxels were examined, one located at the tumor bed and the second distant to the tumor bed. All patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques to 60 Gy. Results : MRS in vivo in patients after brain tumor surgery revealed a statistically significant decrease in the NAA/Cr ratio and increases in the choline/creatine (Cr), choline/NAA, and myo-inosytol/Cr ratios. The intensive signals of lactate and lipids appeared in spectrum. Survival correlated strongly with tumor grade and patient age but the strongest prognostic factor was the lactate/NAA ratio. For lactate/NAA values >2.0 (intensive lactate signal) the 1-year survival rate was 20%, and for lactate/NAA values <2.0, the 1-year survival rate was 85%. Conclusion : A new diagnostic tool demonstrated ability to distinguish between patients with a favorable prognosis and those who will die within 1 year.

US-guided implantation of metallic markers for permanent localization of the tumor bed in patients with breast cancer who undergo preoperative chemotherapy.

Metallic markers were implanted with ultrasonographic guidance in 51 malignant breast tumors in 49 patients to tag the tumor bed in anticipation of complete or almost complete response to preoperative neoadjuvant induction chemotherapy before breast-conservation surgery. The markers were the only remaining evidence of the original tumor site in 47% (23 of 49) of the patients preoperatively. This technique effectively addresses the problem of preoperative localization of the tumor bed in complete or nearly complete response of breast cancer to neoadjuvant chemotherapy.

Infectious retrovirus is inactivated by serum but not by cerebrospinal fluid or fluid from tumor bed in patients with malignant glioma.

Intravenous gene transfer using recombinant retroviruses tends to suffer from a low infectious viral titer when conducted in vivo. This is, in part, caused by complement‐mediated proteolytic inactivation of the retrovirus in human serum. However, if the retroviruses were directly injected into the brain, they might not be inactivated. Supernatant from amphotropic retrovirus‐producing cells harboring the BAG vectors was incubated with sera or cerebrospinal fluid (CSF) of patients with gliomas or unrelated disorders. The retroviruses were severely inactivated in sera. However, no such inactivation was noted in CSF or fluid from the tumor bed of glioma patients. These data suggest that gene transfer using recombinant retroviruses could be done into the cavity after removal of the tumor in glioma patients.

Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy

Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.