Future direction of neoadjuvant therapy for breast cancer.
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Antibodies, Monoclonal↗
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Results for “Neoadjuvant therapy”
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[Neoadjuvant therapy in advanced carcinoma of the esophagus: prognostic value of the histopathological response].
The purpose of this study was to determine the prognostic value of the histopathological response to preoperative radio-chemotherapy in patients with locally advanced oesophageal cancer. Among the 57 patients included in this open prospective study, the disease-free cervical of 48 patients who underwent an oesophagectomy was correlated with the histopathological finding. The 5-years probability of disease-free cervical was 22.1%. Cervical of the patients whose tumor had been downstaged to no residual carcinoma or superficial oesophageal carcinoma was significantly shorter than that of patients with superficial oesophageal carcinoma at presentation treated during the same period (35% vs 57%). Univariate analysis could identify 4 prognostic variables after induction therapy: adenocarcinoma, macroscopic, residual tumor, invaded oesophageal stump, and lymph node involvement. After multivariate analysis according to the Cox model, the remaining independent predictors of recurrence were: adenocarcinoma, invaded oesophageal stump, and lymph node involvement.
Adult↗
[Neoadjuvant therapy in carcinoma of esophagus].
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Combined Modality Therapy↗
Pseudomyxoma ovariilike posttherapeutic alteration in prostatic adenocarcinoma: a distinctive pattern in patients receiving neoadjuvant androgen ablation therapy.
Neoadjuvant combination endocrine therapy that uses leuprolide and flutamide may result in various histologic changes in nontumoral and cancerous prostatic tissues. Posttreatment pseudomyxoma ovariilike change in prostatic adenocarcinoma is a distinctive alteration that may be the only evidence of regressed tumor and can be potentially confused with mucinous carcinoma. We studied 53 clinically localized prostatic adenocarcinomas after 3 to 5 months of treatment with leuprolide and flutamide. Alterations in prostatic adenocarcinoma in posttreatment radical prostatectomy specimens were assessed and compared with pretreatment needle biopsies. All radical prostatectomy specimens exhibited previously well-characterized therapy-associated changes in benign and malignant elements. Thirteen (20%) cases exhibited a distinctive alteration not seen in pretreatment needle biopsies that consisted of minute to large pools of extravasated secretions that resembled pseudomyxoma ovarii and that dissected through prostatic stroma with an infiltrative appearance when viewed at low power. Associated recognizable tumor was present in 10 of 13 (77%) of these cases. Secretions were basophilic in routine sections and contained occasional degenerated cells. Rare pancytokeratin positive cells were seen at the secretion/stroma interface with uniformly negative staining for the high molecular weight keratin 34 beta E-12. The secretions were periodic acid-Schiff positive after diastase digestion and were mucicarminophilic and reactive with Alcian blue at a pH of 2.5. These foci comprised < 5% of the tumor in 5 cases and 5-40% in 5 cases. In 3 cases, 1-2 foci < 1.0 mm exhibited the pseudomyxoma ovariilike changes and were the only evidence of treated tumor. There was no correlation between the presence of pseudomyxomalike change and dose/duration of neoadjuvant therapy, postprostatectomy clinical follow-up, original or final Gleason pattern/score, or pathologic stage. Pseudomyxoma ovariilike change consists of extravasated acid mucin, lacks prostatic basal cells, often occurs in intimate association with residual prostatic adenocarcinoma in posttreatment radical prostatectomy specimens, and probably represents tumor regression as a result of tumor cell attrition secondary to androgen ablation.
Adenocarcinoma↗
Neoadjuvant endocrine therapy models.
Neoadjuvant therapy is therapy administered before surgical intervention and while the tumor remains in the breast. It may be given to treat large, locally advanced tumors, with the aim of shrinking them and thus making their surgical excision either simply possible or less radical. Most neoadjuvant therapy is chemotherapy, but adjuvant endocrine therapy is increasingly used in hormone-sensitive tumors; for example, those responsive to tamoxifen. Repeat biopsies aimed at assessing response to treatment--for example, by examining estrogen receptor status or markers of proliferation in tumor tissue--may be taken during the course of adjuvant therapy. In this chapter, the essential protocols associated with designing neoadjuvant trials are described, methods of assessing response to neoadjuvant therapy are detailed, and various approaches to collecting appropriate clinical samples and their assessment are presented.
Biopsy↗
[Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?].
Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.
Antineoplastic Combined Chemotherapy Protocols↗
Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure.
BACKGROUND: We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. METHODS: Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. RESULTS: The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the "nadir plus 2" definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. CONCLUSION: Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.
Adenocarcinoma↗
Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials.
Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy "curable" disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a "cell cycle response" is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.
Antineoplastic Agents, Hormonal↗
Microwave Thermoablation for Localized Prostate Cancer After Failed Radiation Therapy: Role of Neoadjuvant Hormonal Therapy.
The treatment of residual prostate cancer after irradiation is often associated with significant morbidity and a high failure rate. Percutaneous transperineal interstitial microwave thermoablation is a minimally invasive procedure used experimentally in our institution to treat selected patients with failures of external-beam radiation therapy for prostate cancer. The aim is to ablate all residual intraprostatic cancer thermally. Patients were treated under general or epidural anesthesia with transrectal ultrasound guidance of transperineal placement of the microwave antennas. The rectum, urethra, and a developed space between the prostate and surrounding tissues were actively cooled. The minimal target temperature of the prostate was 65 degrees C for 15 min. The temperature was measured in all cases with interstitial prostatic thermosensors and in selected cases with online magnetic resonance scanning. Thirty-seven patients with apparently localized prostate cancer after failure of treatment for cure with external-beam therapy were subjected to this treatment, and 20 of these patients have at least 12 months of follow-up. The initial prostate specific antigen (PSA) concentration ranged from 0.2 to 120 ng/mL. At 12 months, 12 of 20 patients had no biochemical or histologic evidence of disease, and 11 of 14 patients with initial PSA concentration <10 ng/mL had no evidence of disease. Five of the thirty-seven patients were treated with 3 months of neoadjuvant androgen ablation because the volume of their prostates precluded adequate heating. The average volume decline was 28%, which allowed all men to be treated. Two of these patients have been followed for at lease 1 year, and neither shows evidence of recurrence. Side effects of treatment in all patients were modest. Preliminary results suggest that this treatment might be useful in selected patients as a salvage therapy after failure of radiation therapy for localized prostate cancer.
Journal Article↗
Neoadjuvant hormonal therapy in the management of prostate cancer: a surgical and radiation therapy review.
Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy is an old concept that has recently been revisited. First described in the 1940s as a method to downstage inoperable prostate cancer prior to perineal prostatectomy. NHT fell out of favor for several reasons: the side effects of estrogen therapy, the finality of orchiectomy, improved staging methods, and newer treatment strategies for prostate cancer, including external beam and interstitial radiation therapy. Contemporary interest in NHT has resurfaced primarily due to the introduction of well-tolerated reversible androgen blockade. High cause-specific survival rates following radical prostatectomy for organ confined disease are possible, yet the disturbingly high incidence of positive margins in current radical prostatectomy series led to interest in offering NHT to patients prior to radical prostatectomy to impact on the positive margin rate. Initial nonrandomized studies showed that NHT provided a substantial decrease in prostate size and PSA level in addition to reducing positive margin rate by an uncertain mechanism. Subsequently, controlled randomized studies have been performed, the majority of which have confirmed decreased margin positivity. NHT has been incorporated successfully into external beam radiotherapy for locally advanced prostate cancer as well. Significantly improved disease control is possible when hormones are combined with radiation therapy. The favorable outcome of this radiation therapy approach has led to the approval of flutamide (Eulexin) for this indication when combined with a luteinizing hormone-releasing hormone analogue or orchiectomy. Whether these initial results will ultimately affect recurrence and survival data is unknown. This article provides a comprehensive review of the world literature on NHT: from an historical prospective to the current state of the art for both radical prostatectomy and external beam radiation therapy.
Antineoplastic Agents, Hormonal↗
The case for neoadjuvant androgen suppression before radiation therapy.
Neoadjuvant androgen suppression (NAS) can reduce the number of tumor clonogens prior to radiation, thus increasing the tumor control probability. Also, NAS may sensitize tumor cells to radiation if cell kill by both modalities follows a common pathway. The timing and sequence of NAS and radiation are important, with radiation being most effective if given at the point of maximal tumor regression. The biologic rationale for NAS + radiation has been reinforced by results from randomized trials, in particular RTOG 8610. However, many murine adenocarcinomas respond to androgen deprivation by a reduction in the proliferation rate and arrest in G(0), and in vitro data suggest that this arrest may interfere with radiation-induced cell killing. The mechanism of cell killing after low-dose-rate radiation (brachytherapy) may be different from that after high-dose-rate treatment. There are no reported experimental data assessing the interaction of NAS and brachytherapy to determine whether the combination offers a theoretical advantage or is potentially deleterious. Whether we understand the mechanism or not, clinical trials seem to support a positive interaction of NAS with external-beam radiation, but we have only begun to explore the timing and sequence that will provide the maximal effect. It cannot be assumed that the same advantage will hold with brachytherapy.
Adenocarcinoma↗
Current trends in the management of carcinoma penis--a review.
UNLABELLED: AIMS AND INTRODUCTION: To review the current literature, recent advances and recent trends in the management of squamous cell carcinoma of the penis so as to have a broad overview of penile cancer and its current management. The review was considered keeping in mind that squamous penile carcinoma is an infrequently encountered malignancy and that the etiology is still unclear though certain predisposing conditions are known to exist and also that controversy still exists as to the appropriate management of inguinal adenopathy. We also reviewed the etiological factors, clinical presentation, diagnosis, staging, prognostic factors in addition to management and prophylaxis. METHODS: A literature search was carried out from Pubmed for indexed articles published over the last 50 years using the key words 'Management penile carcinoma', 'Squamous cell carcinoma penis' and 'inguinal lymphadenectomy'. RESULTS: The search yielded over 1500 indexed published articles and reports. Important major reports and studies were reviewed, screened and tracked for recent changes and trends in the management of penile cancer. These were analyzed, tabulated and discussed. CONCLUSIONS: Newer approaches to the management of penile cancer include use of laser, photodynamic therapy, neoadjuvant therapy and sentinel node mapping by lympho-gamma-scintigraphy. The current approach towards managing inguinal adenopathy shows an increasing trend towards the use of these newer modalities as well as the use of certain modifications in lympadenectomy such as (the use of ligasure, modified dissection, saphenous vein sparing and lymphoscintigraphy, etc.) thereby making the procedure considerably less morbid than before.
Carcinoma, Squamous Cell↗
Perspectives on Chemotherapy of Head and Neck Cancer.
Conventional chemotherapy in head and neck cancer is confined to advanced recurrent disease not amenable to surgery or irradiation. The last decade has seen the development of combination chemotherapy programs resulting in improved response rates and the achievement of more complete clinical remissions, although overall survival has not been extended. These same treatments have demonstrated higher regression rates in untreated patients and a survival benefit for the complete responders to induction or neoadjuvant therapy. Neoadjuvant treatment appears to have an important role in laryngeal preservation resulting in improved quality of life. For patients with unresectable cancers of the head and neck, concomitant chemotherapy and radiation gives some survival advantage, albeit with an increase in toxicity. The incidence of these neoplasms may be capable of being decreased with biologic modifiers in some high-risk populations.
Journal Article↗
Clinical presentation of stage IIIA (N2) non-small cell lung cancer: role of multimodality therapy.
Neoadjuvant chemotherapy before surgical resection of locally advanced non-small cell lung cancer (NSCLC) has been shown to improve survival compared with surgery alone in several randomized clinical trials. A case report is presented describing the use of paclitaxel and carboplatin in a multimodality regimen for a patient with stage IIIA N2 NSCLC. Studies are ongoing to determine the optimal type and timing of chemotherapy.
Adenocarcinoma↗
Pathological assessment of rectal carcinoma after preoperative therapy.
Increasingly neoadjuvant therapy is being used to improve outcomes in patients with rectal carcinoma in which the circumferential resection margins are considered to be at risk for involvement if primary surgery were to be undertaken. Assessment of the response to this approach relies on radiological examination, particularly magnetic resonance imaging (MRI) studies. Following definitive surgery, careful histological examination allows full assessment of the tumour response to these preoperative approaches. Histological examination requires careful fixation, examination of the entire area occupied by the tumour prior to down-staging and careful lymph node harvesting. Adequate fixation helps in these endeavours and the lymph node harvest appears to be unaffected by neoadjuvant chemo- or radiotherapy. Correlation between preoperative assessment of response by MRI and the subsequent histological assessment is close, but the presence of isolated residual neoplastic glands in a post-treatment fibrotic stroma is impossible to detect prior to resection. The clinical significance of these microscopic foci remains uncertain, particularly in view of the prolonged tumour doubling time associated with colorectal adenocarcinoma. The preoperative discussion with the patient requires a synthesis of their own scan results and the experience of detailed clinico-pathological studies. While MRI frequently predicts the presence or absence of residual tumour the possibility of under-staging remains and this is of crucial importance if a 'watch and wait' policy is to be adopted following apparent complete clinical and radiological remission. The significance of potential residual microscopic disease in patients with apparent radiological complete remission needs further investigation but may need to be interpreted in individual patients in the context of overall life-expectancy.
Drug-Related Side Effects and Adverse Reactions↗
[Neoadjuvant treatment of rectal cancer: towards an individualised therapy].
Neoadjuvant radiation or chemoradiation followed by oncological resection is the current treatment of choice for locally advanced rectal cancer. Profound diagnostics are mandatory to stratify patients for neoadjuvant treatment or primary surgery. Here, magnetic resonance tomography most probably will become the standard modality due to its ability to predict involvement of the circumferential resection margin during surgery. While the initiation of chemoradiation in T4 rectal cancer and patients with distal tumours potentially undergoing sphincter-preserving surgery is unequivocal, the treatment of choice for the remaining patients is undecided. Here, short-term radiotherapy (5 x 5 Gy) competes with chemoradiation of different intensity. In surgical oncology, minimally invasive surgery of the rectum needs further evidence before it can be accepted as an equivalent. Finally, the increase in multimodality treatment will ultimately increase the incidence of late functional sequelae which, up to now, are underrepresented in most reports due to the priority of oncological results. Since responders to neoadjuvant treatment are the ones who benefit most from these therapies, research related to prediction of treatment response has a fundamental role.
Chemotherapy, Adjuvant↗
[Neoadjuvant hormonal therapy for prostate cancer].
Preoperative neoadjuvant hormonal therapy is still controversial. This therapy's purpose is downstaging prostate cancer at radical prostatectomy and thereby improving the prognosis of prostate cancer. It has been repeatedly demonstrated that hormonal therapy causes significant alterations in the gross and microscopic appearance of the prostate. Most studies report a significant improvement in surgical margins and downstaging. However, it remains to be seen if the favorable findings lead to an improved outcome after radical prostatectomy. Our study showed 6-12 months neoadjuvant hormonal therapy with maximal androgen blockade did not lead to the improved result in long term follow-up. Because, PSA failure was observed 25% of the cases which received neoadjuvant hormonal therapy prior to radical prostatectomy.
Aged↗
Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer.
Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.
Androgen Antagonists↗