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Results for “Pathologic response”

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PubMed1994

Adenocarcinoma of the esophagus and gastroesophageal junction. Clinical and pathologic assessment of response to induction chemotherapy.

A preoperative induction chemotherapy regimen consisting of two monthly courses of etoposide, doxorubicin, and cisplatin was given to 13 patients with nonmetastatic adenocarcinoma of the distal esophagus or gastroesophageal junction. Esophageal ultrasound examination was performed both before chemotherapy and again before surgery. Induction chemotherapy was poorly tolerated with 10 of the 13 patients experiencing at least one episode of severe neutropenia. Two of the 13 patients refused the second course of treatment. A symptomatic response to chemotherapy, defined as a reduction in the presenting symptom, was noted in 10 of the 13 patients (77%). Endoscopic improvement occurred in 9 of the 13 patients (69%). Esophageal ultrasound evidence of a reduction in either T or N stage was noted in only 2 of the 13 patients (15%), however, and neither of these responses was confirmed pathologically. Clinical evidence of disease progression was noted in 4 patients during chemotherapy. With a median follow-up of 31 months, the relapse-free and overall survivals are 25% and 31%, respectively. Despite significant toxicity, our chemotherapy regimen would be considered successful if assessed by symptomatic or esophagoscopic improvement. Esophageal ultrasound, careful pathologic staging, and our disappointing survival rates, however, suggest limited, if any, value for this approach.

Adenocarcinoma↗

PubMed2002

Phase II study of gemcitabine and cisplatin in chemonaive patients with advanced epithelial ovarian cancer.

This phase II study evaluated the activity of gemcitabine (Gemzar) plus cisplatin (Platinol) as first-line treatment of advanced epithelial ovarian cancer. Forty-two chemonaive patients with advanced (stage III and IV) epithelial ovarian cancer received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, up to eight cycles. The median number of cycles completed was 5 (range 2-8). Of the 41 patients evaluable for tumor response, 20 had a partial response and nine had a complete response, for an overall clinical and pathologic response rate of 70.7% (95% CI 56.8-84.6%). Median overall survival for all 42 patients was 23.4 months (95% CI 15.9-29.9 months) and the median progression-free survival time was 10.4 months (95% CI 9.4-13.5 months). The combination was generally manageable. Hematologic toxicity (grade 3/4 neutropenia: 31.0/21.4%; grade 3/4 thrombocytopenia: 9.5/4.8%; grade 3/4 anemia: 11.9/0%) and nausea and vomiting (grade 3/4: 35.7/31.0%) were the most common toxicities. There was one toxic death (septic shock due to hematologic toxicity-induced infection). We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials with the addition of gemcitabine to first-line treatment appear warranted.

Adult↗

PubMed2004

'Quick course' neoadjuvant chemotherapy with cisplatin, bleomycin and vincristine in advanced cervical cancer.

To evaluate the response and safety of 'quick course' neoadjuvant chemotherapy, 30 patients with advanced squamous cell carcinoma of cervix were given cisplatin, bleomycin, and vincristine weekly for 3 courses. The response was evaluated by subjective parameters and by standard response criteria. In addition to the marked improvement in symptoms, the overall objective response was 60% with a complete pathological response of 6.6%. Tumor volume decreased significantly (p=0.002) after chemotherapy. Patients with stage IB and 27% (3 of 11) of patients with stage II disease who became technically stage IB (stage reduction) after chemotherapy underwent surgery. Radiotherapy was given to the remaining patients. All patients tolerated the chemotherapy.

Adult↗

PubMed1993

Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

PURPOSE: The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS: Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS: A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION: High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.

Adenocarcinoma↗

PubMed2002

Inhibition of human CD4(+)CD25(+high) regulatory T cell function.

CD4(+)CD25(+high) T cells are potent regulators of autoreactive T cells. However, it is unclear how regulatory CD4(+)CD25(+high) cells discriminate between desirable inflammatory immune responses to microbial Ags and potentially pathologic responses by autoreactive T cells. In this study, an in vitro model was created that allowed differential activation of regulatory CD4(+)CD25(+high) and responder CD4(+) T cells. If CD4(+)CD25(+high) regulatory cells were strongly activated, they maintained suppressive effector function for only 15 h, while stimulation with weaker TCR stimuli produced regulatory cells that were suppressive until 60 h after activation. In contrast, strongly activated CD4(+) responder T cells were resistant to regulation at all time points, while weakly stimulated CD4(+) cells were sensitive to suppression until 38 or 60 h after activation depending upon the strength of the stimulus. The extent of suppression mediated by CD4(+)CD25(+high) cells also depended on the strength of stimulation in an Ag-specific system. Thus, the stronger the TCR signal, the more rapidly and more completely the responder cells become refractory to suppression.

Antigens↗

PubMedDate not supplied

Chemotherapy with vinorelbine, cisplatin and continuous infusion of 5-fluorouracil in locally advanced breast cancer: a promising low-toxic regimen.

Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-six patients with a T4 breast cancer presentation (eight also had synchronous distant metastases) were treated with V (20 mg total dose i.v. on day 1 and day 3), P (60 mg/m2 i.v. on day 1) and 5-Fu (200 mg/m2/d as continuous infusion) all given every 3 weeks for a maximum of 6 courses. Eleven patients had an inflammatory breast lesion, 4 had a T4a and 11 a T4b presentation. Among those with metastases, 6 had one site and 2 had two sites of disease. After chemotherapy all tumors except one became operable. Objective response was observed in 19 out of the 26 evaluable patients (73%; 95% CI: 52-88%): fourteen had a partial response (54%); 5 had a clinically complete response (19%) and 5 had complete pathological response (20%; 95% CI: 7-41%). Seven patients had stable disease (27%) while no disease progression under treatment occurred. Mild or moderate side-effects included neutropenia (G1-G2 in 58% and G3 in 31% of patients), anemia (G1 in 19%), nausea and/or vomiting (G1-G2 in 92% of patients), mucositis (G1-G2 in 23%), diarrhea (G1 in 19%), plantar-palmar erythema (G1 in 12%) and alopecia G1 in 27% of patients. We conclude that the ViFuP regimen is well-tolerated and its use results in a high response rate. Thus ViFuP may be considered a relevant alternative to more toxic regimens, with an acceptable response rate. Despite the lack of a formal demonstration of equal efficacy with more toxic regimens commonly applied in locally advanced breast cancer, testing new modalities or drugs might provide a more fruitful strategy for relevant therapeutic progress.

Adult↗

PubMed2005

[Response rates following neoadjuvant chemotherapy and breast preserving treatment in patients with locally advanced breast cancer].

INTRODUCTION: The neoadjuvant chemotherapy is increasingly being used in the treatment of patients with locally advanced breast cancer. We describe the hypothesis of the biological behaviour of breast cancer supporting the reason for the existence of this treatment. The improvement of neoadjuvant chemotherapy is being discussed as well as the advantages, disadvantages and problems of the treatment. THE AIM OF EXAMINATION: To study the results of neoadjuvant chemotherapy in patients with locally advanced breast cancer and the proportion of breast preserving surgery after the treatment. METHODS: Sixty seven patients were given neoadjuvant chemotherapy treatment between 01.01.1999 and 12.31.2003. Twenty three patients were stage III A while 35 stage III B and 9 stage III C. 63% of the patients received CEF chemotherapy and 19% were given MMM. 18% were given neoadjuvant Taxotere + Carboplatin and 4% were given Taxotere + Farmorubicin chemotherapy. RESULTS: After neoadjuvant chemotherapy 5 patients had SD (stable disease), 32 patients had MR (minor response) and in 28 cases patients had PR (partial response). Two patients showed pCR (complete pathologic response). Twenty patients (30%) had breast preserving surgery. CONCLUSIONS: On the basis of our own experience neoadjuvant therapy is justified in patients with locally advanced breast cancer as they have bigger chance for breast preserving surgery. If mastectomy and axillary block dissection has to be carried out they are easier to perform. Taxans must be introduced for neoadjuvant treatment in order to improve our results. A longer follow-up is necessary before drawing final conclusions.

Adult↗

PubMed1987

Induction chemotherapy as initial treatment for advanced head and neck cancer: a model for the multidisciplinary treatment of solid tumors.

The role of chemotherapy in the management of patients with SCCHN has not been adequately defined. For patients with recurrent or metastatic disease, several single agents can induce significant tumor regression in 20% to 40% of cases and provide palliation for the individual with a symptomatic or life-threatening lesion. However, complete or long-term control of tumor with chemotherapy alone remains poor. In addition, current regimens of combination chemotherapy have not proved superior to single agents in this setting. Thus, the routine use of combination chemotherapy for patients with metastatic or recurrent SCCHN cannot be justified outside an investigational study. New single agents of promise must be sought and more active combinations of chemotherapy devised for the treatment of patients with metastatic or recurrent SCCHN. Strategies for drug development include the investigation of cisplatin analogues, such as iproplatin and carboplatin, the exploitation of potentially synergistic drug schedules, and the administration of chemotherapy by continuous infusion. That the use of continuous-infusion drug delivery can enhance antitumor activity and limit toxicity for patients with recurrent or metastatic SCCHN was convincingly demonstrated by Kish and co-workers132 in a randomized trial of cisplatin with either bolus or continous-infusion 5-fluourouracil. The antitumor activity of combination chemotherapy may also be increased by the use of mid-cycle nonmyelosuppressive agents, such as methotrexate with leucovorin rescue, or the administration of alternating cycles of non-cross-resistant regimens of combination chemotherapy. The optimal use of chemotherapy in the multidisciplinary treatment of patients with previously untreated SCCHN must also be clarified. Uncontrolled studies of induction chemotherapy report increasingly positive results. Several regimens of induction combination chemotherapy are now associated with significant tumor regression in 70% to 90% of patients, and complete clinical regression of tumor in 20% to 50%. Of patients with a complete clinical response to induction chemotherapy, a complete pathologic response has been documented in 30% to 70% of patients who undergo surgical resection after chemotherapy. It is now evident that patients achieving a complete response to induction chemotherapy have a high probability of local-regional control of tumor and cure. Conversely, patients not responding to induction chemotherapy fare poorly regardless of subsequent local treatment, and it may be appropriate to defer excessively morbid surgical procedures in this patient populus.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗

PubMed1985

Six-drug chemotherapy (hexamethylmelamine, doxorubicin, cisplatin, cyclophosphamide, methotrexate, and 5-FU; CHAMP-5) for ovarian carcinoma: alternating sequences of combination regimens.

Twenty-five patients with previously untreated adenocarcinoma of the ovary (International Federation of Gynecology and Obstetrics, stages II, III, and IV) were placed on a six-drug trial (CHAMP-5) for 18 months. This trial consisted of 28-day cycles of hexamethylmelamine, doxorubicin, and cisplatin alternating with hexamethylmelamine, cyclophosphamide, methotrexate, and 5-FU. After a minimum follow-up of 31 months, 14 (56%) of the 25 evaluable patients achieved complete or partial response and nine (36%) achieved complete pathologic response. Although CHAMP-5 is effective in the treatment of ovarian cancer, the results in these patients are not substantially different from those achieved with hexamethylmelamine, doxorubicin, and cisplatin alone.

Adenocarcinoma↗

PubMed1995

Demodex neomydis sp. n. (Acari: Demodecidae) from the hair follicles of the Mediterranean water shrew, Neomys anomalus (Insectivora: Soricidae).

Demodex neomydis sp. n. from the Mediterranean water shrew, Neomys anomalus, is described as a new species in all developmental stages. This demodecid is classified as a member of the genus Demodex Owen, 1843, but shows several morphological characters described in Soricidex dimorphus Bukva, 1982 and which are absent or very infrequent in other known Demodex species, viz., in the adult stage, a pair of shelf-like lamellae on the dorsum of the podosoma, dorso-lateral extension of the podosoma over the basal part of the gnathosoma, multiple opisthosomal organ in the male, and podosomal position of the vulva in the female. Immature stages of D. neomydis have unusual inflated idiosoma and dorsad deflected gnathosoma. All developmental stages of D. neomydis were found in the lumen of the hair follicles on the host's muzzle, causing no gross pathological response. On histological level, the main pathological change was distension of infested hair follicles by accumulations of up to a dozen mites, which appear to feed on the epithelial cells of the hair follicle walls.

Animals↗

PubMed2002

[Chemoradiation therapy for esophageal cancer].

The current status and future prospects of chemoradiation therapy (CRT) for esophageal cancer are reviewed herein. In Western countries, CRT is performed for every stage of esophageal cancer and it has been reported that in definitive CRT series the complete response rate is 30 to 50%, the mean survival rate more than twelve months, and the in 2-year survival rate about 30%, while in neoadjuvant CRT series the pathological response rate is 20 to 50%, the mean survival period more than twenty months, and the 3-year survival 30 to 40%. On the other hand, as esophageal cancer is treated mainly by surgery in Japan, CRT is applied in patients with tumors invading adjacent organs, and a high pathological complete response rate is reported in some neoadjuvant studies. Although both definitive and neoadjuvant CRT increases the response rate and improves local tumor control, CRT is associated with substantial mortality and morbidity, especially in neoadjuvant series. More effective and less toxic CRT regimens, using new chemotherapeutic agents such as nedaplatin and paclitaxel and new irradiation protocol such as accelerated hyperfractionation, are needed to improve the prognosis of patients with advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

PET/CT in the evaluation of response to treatment of liver metastases from colorectal cancer with bevacizumab and irinotecan.

The present approach at our institution for the treatment of patients with colorectal (CRC) cancer and with liver metastases planned for metastasectomy is the neoadjuvant administration of Bevacizumab with Irinotecan based therapy. Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and simultaneous anatomic localization provided by low-dose non-enhanced computed tomography (CT), can be obtained in a combined modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible contribution of FDG-PET/CT as a surrogate marker to evaluate treatment response of liver metastases in vivo. This is a retrospective evaluation of 18F-FDG PET and CT findings in the first seven consecutive patients. FDG-PET/CT scans were performed before the start of the neoadjuvant and after four cycles of therapy, just prior to surgery. Results were compared to concurrent contrast-enhanced CT, when required, and pathology. Response to treatment was determined according to RECIST size criteria obtained from data from thin (3-5mm) slice CT, and changes in uptake of 18F-FDG uptake on PET. A total of 20 liver lesions were evaluated in seven patients. Overall, 6/7 patients had favorable response to treatment, and only one had progression of disease. One patient was found to be inoperable at surgery. Biopsy was obtained in 1/4 lesions in this patient, while pathology was unable for the remaining three lesions. As such, pathologic validation of findings was available for 17/20 lesions. Complete response (CR) was evident on FDG-PET in 10/17 (58%) lesions, whereas only 4/17(23%) were deemed CR by CT. Similarly, only 1/17 (6%) lesion appeared stable by FDG-PET criteria, whereas three (18%) were termed stable disease (SD) according to size on CT. FDG-PET findings correlated better than CT with pathology, and were more indicative of pathology. Overall PET/CT correctly predicted necrosis at pathology in 70% vs. 35% by CT. Our results suggest that 18F-FDG PET may be instrumental for predicting the pathologic response to Bevacizumab based therapy.

Adult↗

PubMed2025

Neoadjuvant Immunotherapy Promotes the Formation of Mature Tertiary Lymphoid Structures in a Remodeled Pancreatic Tumor Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressing cancer that responds poorly to immunotherapies. Intratumoral tertiary lymphoid structures (TLS) have been associated with rare long-term PDAC survivors, but the role of TLS in PDAC and their spatial relationships within the context of the broader tumor microenvironment remain unknown. In this study, we report the generation of a spatial multiomic atlas of PDAC tumors and tumor-adjacent lymph nodes from patients treated with combination neoadjuvant immunotherapies. Using machine learning-enabled hematoxylin and eosin image classification models, imaging mass cytometry, and unsupervised gene expression matrix factorization methods for spatial transcriptomics, we characterized cellular states within and adjacent to TLS spanning distinct spatial niches and pathologic responses. Unsupervised learning identified TLS-specific spatial gene expression signatures that are significantly associated with improved survival in patients with PDAC. We identified spatial features of pathologic immune responses, including intratumoral TLS-associated B-cell maturation colocalizing with IgG dissemination and extracellular matrix remodeling. Our findings offer insights into the cellular and molecular landscape of TLS in PDACs during immunotherapy treatment.

Humans↗

PubMed2000

Preoperative ECF chemotherapy in gastro-oesophageal adenocarcinoma.

Epirubicin, cisplatin and continuous 5-fluorouracil (5-FU) infusion (ECF) has been reported to result in high clinical response rates in advanced gastro-oesophageal adenocarcinoma and is currently the 'gold standard' chemotherapy regimen for this tumour site. Despite this, its role as preoperative (neoadjuvant) treatment is unproven and therefore remains under investigation. We report our experience using ECF (intravenous epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks, with continuous infusion of 5-FU 200 mg/m2 per day) as preoperative treatment in locally advanced adenocarcinoma of the lower oesophagus, gastro-oesophageal junction and stomach. Of the 23 patients treated (median age 54 years), 19 had potentially resectable disease, four were unresectable and seven had radiological evidence of lymph node involvement. A median of four cycles of ECF was delivered (range 1-6). Ten of 12 patients (83%) with dysphagia reported improvement of symptoms. Clinical disease progression occurred in six patients (26%) during chemotherapy. WHO grade 3 or 4 toxicity occurred in six patients (26%): four haematological, one mucositis, one vomiting. Seventeen patients (74%) proceeded to surgery; 14 (61%) were resected and three were unresectable. There were two (12%) postoperative deaths from respiratory failure. Major pathological response was seen in three patients (13%): one pathological complete response, two microscopic residual disease. Two patients had Stage II (T2N(0-1)) disease and nine were Stage III (T(3-4)N(0-1)). None of the patients with initially unresectable disease was rendered resectable. After a median follow-up interval of 33 months (range 26-53), the overall median survival was 12 months and 2-year survival was 30%. All patients who were initially unresectable or had radiological evidence of lymph node involvement have died. Therefore, despite good symptomatic response rates, ECF chemotherapy given in the preoperative setting did not appear to improve the outcome of patients with unresectable or radiologically lymph node-positive gastro-oesophageal adenocarcinoma. The role of ECF chemotherapy in resectable tumours is unclear and is currently under investigation in the randomized MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) study.

Adenocarcinoma↗

PubMed2006

Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography.

PURPOSE: This study aimed to assess prospectively the efficacy of sequential [18F]fluorodeoxyglucose positron emission tomography (FDG PET) to evaluate early response to neoadjuvant chemotherapy in stage II and III breast cancer patients. PATIENTS AND METHODS: Images were acquired with a PET/computed tomography scanner in 64 patients after administration of FDG (5 MBq/kg) at baseline and after the first, second, third, and sixth course of chemotherapy. Ultrasound and mammography were used to assess tumor size. Decrease in the standardized uptake value (SUV) with PET was compared with the pathologic response. RESULTS: Surgery was performed after six courses of chemotherapy and pathologic analysis revealed gross residual disease in 28 patients and minimal residual disease in 36 patients. Although SUV data did not vary much in nonresponders (based on pathology findings), they decreased markedly to background levels in 94% (34 of 36) of responders. When using 60% of SUV at baseline as the cutoff value, the sensitivity, specificity, and negative predictive value of FDG PET were 61%, 96%, and 68% after one course of chemotherapy, 89%, 95%, and 85% after two courses, and 88%, 73%, and 83% after three courses, respectively. The same parameters with ultrasound (US) and mammography were 64%, 43%, and 55%, and 31%, 56%, and 45%, respectively. Assessment of tumor response with US or mammography was never significant whatever the cutoff. CONCLUSION: Pathologic response to neoadjuvant chemotherapy in stage II and III breast cancer can be predicted accurately by FDG PET after two courses of chemotherapy.

Adult↗

PubMed1998

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer.

PURPOSE: To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial. MATERIALS & METHODS: To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This "boost" treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery. RESULTS: Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I & II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p=.04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) > or = 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p=0.017). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p= 0.04). Older age (> or =61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting.

Adenocarcinoma↗

PubMed1996

The role of inflammation in atherosclerosis.

The vascular endothelium serves as a dynamic interface between circulating blood elements and the interstitial tissues. As such, it communicates with cells in the vessel wall as well as with the surrounding tissue, sensing its environment and responding accordingly. The vasculature must maintain a delicate balance when initiating a functional response by producing both pro-inflammatory and anti-inflammatory mediators, vasoconstrictors and vasodilators, growth stimulators and inhibitors, and prothrombotic and anti-thrombogenic factors. Any response to injurious agents could lead to pathologic responses. One response to injury by the endothelium is the new or increased expression of surface receptors for immune elements. In atherosclerosis, the adhesion of monocytes and T cells to the endothelium is a key event triggered by some form of insult. Subsequent events include monocytic infiltration of the vessel wall, alterations in lipid metabolism, and the activation of these cells into foam cells. The presence of large numbers of foam cells in the intima may produce a high concentration of cytokines and growth factors within a localized area, extracellular matrix perturbations, smooth muscle cell proliferation, and ultimately platelet aggregation at the site of stenosis. Endothelial cells will propagate an inflammatory response long after the initial insult to the arterial vessel. Thus, all of the cellular elements of the vessel wall, as well as the atherosclerotic plaque itself, produce adhesive molecules, cytokines and growth factors that amplify and propagate the pathologic process.

Animals↗

PubMed2005

Neoadjuvant docetaxel followed by adjuvant doxorubicin and cyclophosphamide in patients with stage III breast cancer.

BACKGROUND: To evaluate clinical and pathologic response to neoadjuvant docetaxel therapy in patients with stage III breast cancer. PATIENTS AND METHODS: Forty-five patients were planned to receive four cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery, four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) every 3 weeks, radiation therapy (RT), and tamoxifen when indicated. RESULTS: After four cycles of neoadjuvant docetaxel, the clinical response rate within the breast was 59% (95% CI 42% to 73%) and overall (breast and axilla) was 49% (95% CI 38% to 72%) in the intention-to-treat (ITT) population. At the time of surgery, 10% (n=4) of patients had a pathologic complete response (pCR) in the breast, 27% (n=11) had a pCR within the axillary lymph nodes, and 7% (n=3) had a pCR in the breast and axilla (95% CI 2% to 21%). An additional 5% (n=2) had minimal residual invasive tumor (<5 mm). The 5-year overall survival rate was 80%. The percentage of patients with grade 3/4 neutropenia was similar during docetaxel (93%) and AC (86%), while a greater percentage of patients had febrile neutropenia during docetaxel treatment (27%) compared with AC treatment (7%). CONCLUSIONS: Neoadjuvant docetaxel followed by surgery, adjuvant AC, hormonal therapy where indicated, and RT is an active regimen for patients with stage III breast cancer.

Adult↗