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1.
Ann Oncol ; 24 Suppl 8: viii54-viii60, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24131971

ABSTRACT

The diagnostic and local treatment modalities of hereditary breast cancer (HBC) are evolving based on emerging evidence from new imaging, radiotherapy and surgical studies. The optimal selection of diagnostic and therapeutic strategies for the individual HBC patient remains an area of active research in this relatively new patient population. In this context, some rational pathways of intervention are currently available to both reduce cancer risk in mutation carriers without a cancer diagnosis, as well as to reduce the risk of recurrence or new cancers among the carriers already diagnosed with a malignancy. It is encouraging to notice to what degree certain interventions have successfully reduced both the risk of malignancy and the anxiety associated with this genetic diagnosis. This updated report aims at summarizing the most recent findings, while it identifies the areas of uncertainty that remain, and continue to present difficult challenges, particularly among younger HBC patients.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/congenital , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Mutation
2.
Clin Cancer Res ; 7(10): 3025-30, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11595690

ABSTRACT

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. EXPERIMENTAL DESIGN: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Lymphocytes, Tumor-Infiltrating/drug effects , Paclitaxel/therapeutic use , Proteins , Adult , Aged , Apoptosis/drug effects , Breast Neoplasms/surgery , CD3 Complex/analysis , CD8 Antigens/analysis , Chemotherapy, Adjuvant , Female , Humans , Immunohistochemistry , Membrane Proteins/analysis , Middle Aged , Poly(A)-Binding Proteins , RNA-Binding Proteins/analysis , T-Cell Intracellular Antigen-1 , Treatment Outcome
3.
Urology ; 56(3): 453-8, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10962314

ABSTRACT

OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to 54 Gy achieves results comparable to higher doses. We studied the effect of moderate doses of postoperative radiation therapy on urinary continence and sexual potency in prostate cancer patients who had undergone nerve-sparing prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate cancer patients were selected to undergo nerve-sparing prostatectomy. A total of 94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy to the prostatic bed, based on microscopic positive margins, seminal vesicle involvement, and/or Gleason score. Subjective patient reports regarding the potency and urinary continence status were recorded during a semistructured telephone interview at 3 or more years after treatment. The findings in irradiated and nonirradiated patients were compared and correlated to those obtained from the same patients preoperatively and 1 year postoperatively. RESULTS: At 3 or more years of follow-up no significant difference among irradiated and nonirradiated patients was detected. Most patients described optimal urinary continence and approximately one third had maintained potency after bilateral nerve-sparing prostatectomy. None of the patients who had undergone unilateral nerve-sparing surgery remained potent. Using a multivariable analysis, the significant predictors for maintaining potency were the status at 1 year postoperatively and bilateral versus unilateral nerve-sparing procedure. CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy) did not affect the long-term pattern of maintenance of either function.


Subject(s)
Penile Erection/radiation effects , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Urination/radiation effects , Adult , Age Factors , Aged , Aged, 80 and over , Confidence Intervals , Erectile Dysfunction/epidemiology , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prostatectomy/methods , Prostatic Neoplasms/physiopathology , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Urinary Incontinence/epidemiology
4.
Med Phys ; 27(5): 1005-10, 2000 May.
Article in English | MEDLINE | ID: mdl-10841403

ABSTRACT

PURPOSE: To investigate the technical and physical feasibility of using a radiosurgery-like technique to irradiate a small target within the breast with a single fraction. MATERIAL AND METHODS: During diagnostic biopsy, a tantalum surgical clip is placed in the lesion identified at mammography. Transverse CT scans over the entire breast are obtained, as the patient lies prone on a special table that allows the breast to hang down. The clip is used as a reference point to define the isocenter of the radiation treatment. RESULTS: The clip is visible on port films taken with a 4 MV beam, allowing the isocenter to be set to its planned location. No movement of the hanging breast is visually detected. The possible beam directions are enclosed by a 220 degrees horizontal x 180 degrees vertical angular interval. Dosimetry of two "radiosurgical" examples, (A) seven fixed horizontal beams and (B) six 45 degrees arcs and a 90 degrees sagittal arc using a 4 MV x-ray beam with a 32 mm diameter collimator, are discussed. Both field arrangements produce adequate tumor coverage: the minimum target dose is 83% of the dose maximum in the fixed beam arrangement and 86% in the multiarc setup. In arrangement A the lung and other tissues external to the breast receive dose only from scattered radiation. In arrangement B the maximum lung dose is less than 5% of the dose to isocenter. CONCLUSION: From a dosimetric point of view both described techniques are feasible, and the radiosurgery-like treatment is executable.


Subject(s)
Breast Neoplasms/surgery , Radiosurgery/methods , Therapy, Computer-Assisted/methods , Biophysical Phenomena , Biophysics , Breast Neoplasms/diagnostic imaging , Female , Humans , Mammography , Radiographic Image Interpretation, Computer-Assisted , Radiosurgery/instrumentation , Radiosurgery/statistics & numerical data , Therapy, Computer-Assisted/instrumentation , Therapy, Computer-Assisted/statistics & numerical data , Tomography, X-Ray Computed
5.
Ann Surg Oncol ; 7(2): 145-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10761794

ABSTRACT

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/surgery , Mastectomy, Modified Radical , Paclitaxel/therapeutic use , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Feasibility Studies , Female , Humans , Middle Aged , Postoperative Complications , Radiotherapy Dosage , Radiotherapy, Adjuvant , Treatment Outcome
7.
Radiology ; 214(3): 688-92, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10715031

ABSTRACT

PURPOSE: To perform a single-arm study to determine the effectiveness of and potential toxic reactions to local hyperthermia and systemic carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) for the treatment of advanced or recurrent squamous cell carcinomas of the head and neck. MATERIALS AND METHODS: Eight patients with squamous cell carcinoma of the head and neck and stage IV disease (N2 or N3 neck adenopathy) or recurrent local-regional disease and who were previously and definitively treated were included in the study. Thermochemotherapy was administered every 4 weeks. Recorded end points were tumor response, duration of response, incidence of distant metastases, survival, cause of death, and toxic reactions. RESULTS: One patient had a complete response to therapy, and two had a partial response. Five patients had no response or developed progressive disease during therapy. Six patients died after 4-13 months of progressive disease. Two long-term survivors received radiation therapy; one also underwent surgical resection for residual neck disease. Each thermochemotherapeutic session was well tolerated, with minimal discomfort. Toxic reactions included hypotension, vomiting, hyponatremia, anemia, thrombocytopenia, and infection at the site of administration. There were no life-threatening toxic reactions. CONCLUSION: The combined use of hyperthermia and carboplatin shows potential in the management of unresectable head and neck tumors and is safe and well tolerated. Further studies on thermochemotherapy are warranted to assess its potential.


Subject(s)
Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/therapy , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Otorhinolaryngologic Neoplasms/therapy , Aged , Antineoplastic Agents/adverse effects , Carboplatin/adverse effects , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Disease Progression , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Otorhinolaryngologic Neoplasms/mortality , Otorhinolaryngologic Neoplasms/pathology , Palliative Care , Radiotherapy, Adjuvant , Survival Rate , Treatment Outcome
8.
Clin Cancer Res ; 6(12): 4610-7, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11156210

ABSTRACT

The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis , Biopsy, Needle , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Mitosis , Paclitaxel/therapeutic use , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Dose-Response Relationship, Drug , Female , Humans , In Situ Nick-End Labeling , Time Factors , Treatment Outcome
9.
Semin Radiat Oncol ; 9(2 Suppl 1): 34-42, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10210538

ABSTRACT

Few studies have evaluated the role of concurrent chemoradiation therapy in the management of locally advanced breast cancer. The availability of radiosensitizing chemotherapeutic agents that are effective in breast cancer and the encouraging results achieved by concurrent chemoradiation in other malignancies have prompted us to investigate this approach. Paclitaxel is a promising agent for use with concurrent radiotherapy because of its single-agent efficacy profile and its radiosensitizing effects. A clinical protocol of preoperative paclitaxel and radiation in locally advanced breast cancer is ongoing at our institution to test feasibility, measure pathologic response at mastectomy, and explore association of pathologic response with molecular tumor markers. Initially, the study was designed to test weekly paclitaxel at a dose of 60 mg/m2 during radiation therapy, delivered 5 days a week at 200 cGy fractions to a total dose of 50 Gy over 5 weeks. Due to severe skin toxicity in the first two patients, the protocol was amended to change the scheduling of paclitaxel to 30 mg/m2 twice weekly and to reduce the radiation to 180 cGy fractions to a total dose of 45 Gy, delivered 5 days a week over 5 weeks. Presently, 13 patients have been accrued; preliminary data indicate good tolerance to twice-weekly paclitaxel, and four of eight evaluable patients have achieved pathologic response (one patient who received the weekly regimen and three who received the twice-weekly regimen). In addition, sequential fine-needle aspirations of palpable breast cancers were obtained in patients enrolled in a parallel study of preoperative single-agent paclitaxel (200 mg/m2 every 2 weeks, for a total of four cycles before breast surgery). Preliminary results suggest that a steep increase in the mitotic index occurs during the first day after paclitaxel administration and plateaus between the second and the third day, then decreases to pretreatment values. The peak apoptotic index occurs at approximately 72 hours after paclitaxel administration and decreases at approximately 98 hours. These initial findings suggest that twice-weekly dosing of paclitaxel may optimize recruitment of cells into the G2/M phase of the cell cycle, the most radiosensitive phase.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Paclitaxel/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Combined Modality Therapy , Female , Humans , Radiotherapy Dosage
10.
Int J Radiat Oncol Biol Phys ; 39(5): 1053-7, 1997 Dec 01.
Article in English | MEDLINE | ID: mdl-9392544

ABSTRACT

PURPOSE: To acquire preliminary information on the radiosensitivity of the Koch ileal reservoir by reviewing acute and late toxicity incurred by nine patients who received pelvic radiotherapy after cystoprostatectomy with lower urinary reconstruction utilizing a Koch ileal reservoir with bilateral uretero-ileal-urethrostomy. METHODS AND MATERIALS: All patients were irradiated because of synchronous locally advanced prostate cancer (pT3). A fourfield box technique at 100 cm source-axis-distance (SAD) with all fields treated every day at 1.8 Gy daily fractions, to a total dose of 45-50.40 Gy was used. The average AP portal dimension was 11 x 11 cm, and the average lateral was 7 x 8 cm. All portals were shaped using custom shields to optimize protection of normal tissues not suspected of tumor involvement (small bowel, posterior rectal wall). No attempt was made to shield the Koch ileal reservoir. For each patient, comparison of the treatment portals with the Kochgram radiography (gravity cystogram) confirmed the inclusion of the majority of the Koch ileal reservoir within the radiation fields. Acute and late morbidity was measured by RTOG toxicity criteria by retrospectively reviewing the patients' records. RESULTS: Only mild acute toxicity was reported by the patients: Six patients experienced grade 1 acute urinary toxicity and one suffered Grade 2 acute urinary toxicity. In four patients Grade 1 acute gastrointestinal toxicity occurred and in two patients Grade 2 toxicity occurred. With a median follow-up of 50 months late toxicity consisted mainly of microscopic hematuria in six patients and persistent frequency in two patients (with spontaneous improvement respectively at 4 and 6 months after radiation). No patients experienced acute or late Grade 3 or 4 genitourinary or gastrointestinal toxicity. CONCLUSION: The use of moderate doses of pelvic radiotherapy (45-50.40 Gy) at standard fractionation was well tolerated among nine patients who received pelvic radiation for invasive prostate cancer detected at the time of cystectomy and Koch ileal reservoir diversion. These preliminary data support the evidence that patients with a Koch ileal reservoir could safely undergo postoperative pelvic radiotherapy in these dose ranges and fractionation.


Subject(s)
Proctocolectomy, Restorative , Prostatic Neoplasms/radiotherapy , Radiation Tolerance , Urinary Diversion , Aged , Humans , Male , Middle Aged , Radiation Dosage
11.
Int J Radiat Oncol Biol Phys ; 39(5): 1059-68, 1997 Dec 01.
Article in English | MEDLINE | ID: mdl-9392545

ABSTRACT

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Fluorouracil/administration & dosage , Adult , Breast Neoplasms/surgery , Combined Modality Therapy , Disease-Free Survival , Feasibility Studies , Female , Humans , Infusions, Intravenous , Mastectomy, Modified Radical , Middle Aged
12.
Am J Surg ; 174(6): 705-7; discussion 707-8, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9409601

ABSTRACT

BACKGROUND: Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability. METHODS: Eligible patients had locally advanced breast cancer deemed unresectable with primary wound closure. Patients received 8 weeks of infusional 5-fluorouracil (5-FU) 200 mg/m2 per day and radiation therapy to 50 Gy. Patients rendered resectable underwent modified radical mastectomy (MRM) followed up by chemotherapy. RESULTS: Of 30 evaluable patients, 73% had an objective clinical response. All were able to undergo MRM with primary wound closure; 63% had residual disease, 20% had minimal microscopic disease, and 17% had complete pathologic response. Treatment-related toxicity was minimal. Surgical morbidity was not increased. CONCLUSIONS: Infusional 5-FU with concomitant radiotherapy is well tolerated and effective at producing shrinkage in the majority of patients, converting inoperable breast cancer to easily resectable disease.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Breast Neoplasms/surgery , Fluorouracil/therapeutic use , Mastectomy, Modified Radical , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Preoperative Care , Radiotherapy, Adjuvant , Treatment Outcome
13.
Gynecol Oncol ; 65(2): 336-42, 1997 May.
Article in English | MEDLINE | ID: mdl-9159348

ABSTRACT

Radiation therapy is the mainstay in treatment of locally advanced cervical carcinoma. Several chemotherapeutic agents have been used as radiation sensitizers in the treatment of cervical cancer in an effort to improve local response and survival. A prospective study was designed to evaluate carboplatin as a radiosensitizer in advanced cervical cancer. Standard radiotherapy techniques were used to treat patients with Stage IIA-IIIB cervical cancer. Intravenous carboplatin was administered twice weekly concurrent with external beam radiation. Of 22 evaluable patients, there were 19 complete responders of whom 15 remain alive: 11 patients were alive and disease free at last visit for a median duration of 15 months follow-up (range, 4-43 months) and 4 patients remain alive with disease for a median duration of 17 months (range, 3-55 months). Seven have died, one of whom was without evidence of disease. There were no treatment-related deaths and no grade 4 toxicity. The most significant adverse effect was hematologic resulting in four patients with grade 3 neutropenia or anemia. There were no fistulae or late gastrointestinal or genitourinary complications. This pilot study suggests that carboplatin administered with standard radiation is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Pilot Projects , Survival Rate , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
14.
Int J Radiat Oncol Biol Phys ; 35(5): 993-1001, 1996 Jul 15.
Article in English | MEDLINE | ID: mdl-8751408

ABSTRACT

PURPOSE: To investigate the feasibility, toxicity, and pharmacokinetics of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic hyperthermia (HT) in advanced ovarian cancer patients. METHODS AND MATERIALS: Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initial course of i.p. CB for baseline pharmacokinetics followed by three cycles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature > 42 degrees but < 50 degrees C while maintaining normal tissue temperatures < 43 degrees C and systemic body temperatures < 38 degrees C. No analgesic premedication was used. Thermometry was recorded by multisensor fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. RESULTS: Thirteen patients received a total of 31 sessions. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal temperatures > 40 degrees C, for more than 40 min in 7 of 31 sessions. The average values of thermal variables were T90 = 40 degrees C, TAVE = 41 degrees C, TMIN = 38.2 degrees C, and TMAX = 42.9 degrees C. The mean maximum systemic temperature was 38 degrees C. Acute thermal toxicities requiring early interruption of hyperthermia were systemic temperature exceeding 38 degrees C (11 of 31), abdominal pain or generalized distress (20 of 31), and vomiting (2 of 31). Hematological toxicities were not increased by hyperthermia. Pharmacokinetics were consistent with enhanced clearance of CB by HT. Lower radio frequencies (< 75 MHz) achieved better heat deposition in the peritoneal cavity than higher frequencies (> 75 MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with no evidence of disease at 40 and 43 months from treatment. CONCLUSIONS: Intraperitoneal temperatures in the range of 40 degrees C maintained for approximately 40 min can be achieved within the described setting. The probability of successful induction of therapeutic intraperitoneal temperatures appears to be higher when frequencies below 75 MHz are used. Patients who are potentially platinum sensitive and have minimal residual disease could potentially benefit from the combined treatment under the conditions studied. However, this temperature-time range appears inadequate against platinum resistant disease, and/or bulky residual pelvic disease. Alternative approaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed.


Subject(s)
Antineoplastic Agents/adverse effects , Carboplatin/administration & dosage , Hyperthermia, Induced , Ovarian Neoplasms/therapy , Adult , Aged , Antineoplastic Agents/pharmacokinetics , Carboplatin/adverse effects , Carboplatin/pharmacokinetics , Cohort Studies , Combined Modality Therapy , Feasibility Studies , Female , Humans , Injections, Intraperitoneal , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Platinum/metabolism , Treatment Outcome
15.
J Urol ; 155(2): 616-9, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8558674

ABSTRACT

PURPOSE: We analyzed the impact on potency and urinary continence of moderate doses of radiation (45 to 54 Gy.) given postoperatively after nerve sparing prostatectomy. MATERIALS AND METHODS: Between 1983 and 1992, 294 of 762 prostate cancer patients were selected to undergo nerve sparing prostatectomy. Subjective patient reports regarding potency and urinary continence status were obtained preoperatively, 1 year postoperatively or 1 year after completion of radiation. RESULTS: Of the 294 patients 105 received postoperative radiotherapy (45 to 54 Gy.) to the prostatic bed. There were patients with more advanced stages of disease in the irradiated group, including 89% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3), compared to 14% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3) in the nonirradiated group (p < 0.001). No difference in urinary continence was noted in the irradiated (94%) compared to the nonirradiated group (92%, p = 0.64). Of the patients who underwent bilateral nerve sparing prostatectomy 44% who received and 48% who did not receive radiation had recovered potency at 1 year (p = 0.76). Of those who underwent unilateral nerve sparing prostatectomy 10% who received and 33% who did not receive radiation had recovered potency at 1 year (p = 0.14). Using multivariate analysis patient age younger than 63 years and bilateral versus unilateral nerve sparing procedures were significant predictors of potency. CONCLUSIONS: Our retrospective study suggests that at 1 year after treatment moderate doses of postoperative radiotherapy did not have a significant impact on the recovery of urinary continence and potency after nerve sparing prostatectomy. However, longer followup is required to determine the impact of this radiation protocol on long-term preservation of potency after nerve sparing prostatectomy.


Subject(s)
Prostatectomy/methods , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Combined Modality Therapy , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Humans , Male , Middle Aged , Multivariate Analysis , Postoperative Care , Prostate/innervation , Prostatectomy/adverse effects , Radiotherapy/adverse effects , Radiotherapy Dosage , Retrospective Studies , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology
16.
Int J Radiat Biol ; 68(4): 411-2, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7594966

ABSTRACT

Fibroblasts cultured from skin biopsies of patients with AIDS and Kaposi's sarcoma were found to be more radiosensitive than fibroblasts from non-HIV-infected-sources. This supports clinical observations of overt sensitivity to radiotherapy in some AIDS patients with Kaposi's sarcoma.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , Radiation Tolerance , Sarcoma, Kaposi/radiotherapy , Cells, Cultured , Fibroblasts/radiation effects , Humans
17.
Am J Clin Oncol ; 18(4): 331-6, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7625375

ABSTRACT

The outcome of 100 consecutive newly diagnosed breast cancer patients treated between 1975 and 1985 within a protocol of planned segmental mastectomy and radiation therapy that included an initial brachytherapy boost is reported. Margins were not routinely inked in this study and the tumor bed was determined with the operating surgeon at the time of brachytherapy. There were 30 T1 tumors, 61 T2, and 9 T3. Segmental mastectomy was followed 2 weeks later by an interstitial implant with iridium-192 sources given as initial boost dose to the tumor bed, at the time of axillary dissection. All patients received at least 20 Gy as boost dose followed by external beam radiation to a total dose of 45-50 Gy to the breast and regional nodes delivered over a period of 4-5 weeks. With a median follow-up of 7 years a total of 3 (3%) breast recurrences were detected (1/30 in T1 tumors, 2/61 in T2 tumors). Only one of the three recurrences was at the initial tumor bed. None of the nine T3 patients included in this series recurred locally. There were 4 severe complications (2 soft tissue necroses and 2 osteonecroses) occurring in 2/30 T1 and in 2/61 T2. Cosmetic results were good to excellent in 77% of the cases and fair to poor in 23%. The actuarial local control and survival probability rate were, respectively, 95% and 85% at 5 years and 93% and 73% at 10 years. Initial brachytherapy boost to a target volume accurately determined with the operating surgeon followed by subsequent external beam radiotherapy achieved excellent local control in the breast even for lesions larger than 2 cm (70% of the reported cases).


Subject(s)
Brachytherapy , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Mastectomy, Segmental , Middle Aged , Radiotherapy Dosage , Radiotherapy, Adjuvant , Survival Rate
18.
Cancer ; 75(5): 1135-40, 1995 Mar 01.
Article in English | MEDLINE | ID: mdl-7850712

ABSTRACT

BACKGROUND: Radiation therapy plays an important role in the loco-regional control of carcinoma of the cervix. Strict adherence to the radiation protocol, without the introduction of time breaks, has been shown to favorably affect loco-regional control and survival, making adherence a crucial variable for optimal outcome. Because carcinoma of the cervix is a common disease among Latinas, with survival rates worse than those of other ethnic groups in this country, the pattern of adherence to the prescribed radiation treatment among Latina patients seen at Los Angeles County Hospital were studied. METHODS: The records of 69 consecutive Latina patients with cervical cancer who received radiation therapy at Los Angeles County Hospital were reviewed. Semi-structured interviews in a successive group of 30 similar patients were conducted to acquire preliminary information about their psychosocial characteristics. RESULTS: The results demonstrate inferior rates of optimal adherence to radiation treatment among Latina immigrant patients when compared with the rates reported in the literature for the general population of cervical cancer patients in United States (16 vs. 63%). Furthermore, a large subset of patients (20%) in the series elected to discontinue treatment without a medical reason. When a comparable group of Latina patients was interviewed, potential practical, psychologic, and cultural barriers to optimal care were identified. CONCLUSIONS: The results from this exploratory study support the need for further studies to document the pattern of adherence to radiotherapy in the rest of the country among this minority population. The results suggest that an intervention to improve information and adherence to radiation therapy may be necessary to assure Latinas a chance for rates of cure comparable with the national standards.


Subject(s)
Hispanic or Latino/statistics & numerical data , Patient Compliance/psychology , Uterine Cervical Neoplasms/psychology , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Emigration and Immigration , Female , Humans , Interviews as Topic , Middle Aged , Radiotherapy/statistics & numerical data , Uterine Cervical Neoplasms/ethnology
20.
Am J Clin Pathol ; 92(3): 300-7, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2528284

ABSTRACT

Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses.


Subject(s)
AIDS-Related Complex/blood , Acquired Immunodeficiency Syndrome/blood , HIV Seropositivity/blood , Leukocytes/classification , AIDS-Related Complex/pathology , Acquired Immunodeficiency Syndrome/genetics , Acquired Immunodeficiency Syndrome/pathology , Adult , Antigens, Differentiation, T-Lymphocyte/analysis , HIV Seropositivity/pathology , Humans , Immunologic Techniques , Leukocyte Count , Leukocytes/pathology , Lymphocyte Activation , Male , Phenotype , T-Lymphocytes/classification , T-Lymphocytes/pathology , T-Lymphocytes, Helper-Inducer/classification
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