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Results for “Pathologic Complete Response”

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At least 73 records · Page 4Linked to original sources

PubMed1990

Immunohistochemical analysis of P-glycoprotein expression correlated with chemotherapy resistance in locally advanced breast cancer.

We analyzed the expression of P-glycoprotein in samples from 48 patients with locally advanced breast cancer. Tumor samples from 40 patients were obtained at mastectomy, which was performed after three cycles of induction chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone. P-glycoprotein expression distributed focally was observed in 20 tumors by the immunoperoxidase method using the anti-p170-monoclonal antibody C219. The percentage of the tumor cell population expressing P-glycoprotein varied from less than 5% to greater than 30%; expression was observed significantly more often in tumors that showed less than partial response to the preoperative chemotherapy. Furthermore, P-glycoprotein was not expressed in eight tumor specimens obtained at the time of diagnosis, prior to chemotherapy, from patients who subsequently had pathologic complete responses. A comparative study of P-glycoprotein expression before and after chemotherapy and upon recurrence of tumor was done on a limited number of samples. No significant differences in P-glycoprotein expression were found. Therefore, it is possible that an intrinsic, rather than acquired, drug resistance may play a role in the failure of induction chemotherapy for locally advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Prolonged chemotherapy for localised squamous carcinoma of the oesophagus.

We evaluated the feasibility of six courses of chemotherapy in 34 consecutive patients with localised squamous cell carcinoma of the oesophagus. All 32 evaluable patients first received at least two courses of chemotherapy. There were 18 patients with resectable carcinomas who underwent surgery and 14 patients with unresectable carcinomas who received definitive chemoradiotherapy. After two courses of 5-fluorouracil and cisplatin 21 (66%) of 32 patients had either a complete or major response. A median of five courses (range, 1-6 courses) was administered. 17 out of 18 (94%) patients with resectable carcinoma had a 'curative' resection (negative proximal, distal, and radial margins by histopathology in an en-block resection specimen) and 2 patients had a complete pathological response. The median survival duration of all patients was 28 months (range, 2-46+ months). The median survival duration of 14 patients with unresectable carcinoma was 23 months (range, 8-36+ months), and the median survival duration of 18 patients with resectable carcinoma has not been reached at a median follow-up of 24+ months (range, 10+ to 46+ months). No deaths occurred because of chemotherapy or chemoradiation therapy. Our data suggest that prolonged chemotherapy is feasible in patients with locoregional squamous carcinoma of the oesophagus. An ongoing controlled trial will determine the contribution of chemotherapy to patients' survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

A phase I-II trial of intraperitoneal cisplatin and alpha-interferon in patients with persistent epithelial ovarian cancer.

A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2025

Molecular Landscape, Genomic Shift, and Prediction in the Neoadjuvant Setting of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

The amplification or overexpression of human epidermal growth factor receptor 2 (HER2) defines a breast cancer subtype, which benefits from neoadjuvant HER2-targeted therapy. However, at least 40% of patients respond poorly or do not respond to treatment. We analyzed the main genomic alterations of 64 HER2+ patients by next-generation sequencing to identify new predictors of response and correlate them with clinicopathological parameters. We also compared the genomic alterations between primary and residual tumors after neoadjuvant treatment. The TP53 gene was the most frequently mutated gene, and in combination with ERBB2 overexpression, the 2 were predictive of residual cancer burden (P = .001). Furthermore, the combination of their immunohistochemical counterpart (p53 mutant and score 3+ for HER2) can predict complete pathological response and the grade of response (P = .038 and P = .031, respectively). Therefore, p53 could be included in the initial panel of breast cancer biomarkers to help therapeutic decision-making in HER2+ cases.

Humans↗

PubMed1989

Neoadjuvant therapy of squamous cell carcinoma of the esophagus: role of resection and benefit in partial responders.

Twenty-eight patients were treated between 1981 and 1987 with a combination of radiation therapy and two courses of 5-fluorouracil and cisplatin followed by esophageal resection. Sixteen patients (57%) underwent resection. Operative mortality was 6% (1 of 16), and the 15 operative survivors have been followed for more than 23 months. Complete pathological response was achieved in 8 of the 15 patients, and 10 patients (66%) are alive with no evidence of disease; 4 patients (27%) have survived with no evidence of disease for more than 5 years. Four partial responders are alive, and 3 are alive with no evidence of disease for more than 5 years. An aggressive approach with a low mortality has demonstrated survival benefit to complete responders and, contrary to findings of previous reports, has established a role for surgical resection and survival benefit in patients with partial response, with 3 of 7 (47%) patients surviving more than 5 years.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2025

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates ≥50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article↗

PubMed1990

Neoadjuvant chemotherapy in stage X ovarian carcinoma.

Seventeen patients with presumed advanced ovarian cancer were treated initially with platinum-based chemotherapy. All patients had either cytologic or histologic findings consistent with an ovarian adenocarcinoma. Eight patients subsequently had surgery: one patient had a complete pathological response and one patient had microscopic disease; both are alive without evidence of disease. Five patients were surgically debulked to less than 1 cm, and one patient had large residual disease after surgery. Four of these patients are alive with disease and one died of disease. Nine patients did not have surgery; two patients had no response to chemotherapy and four patients had stabilization of disease. These six patients have died. Two patients had initial partial responses and are alive with disease. One patient with a complete clinical response at autopsy was without evidence of disease. The follow-up ranged from 7 to 109 months; the median survival was 15 months. Comparison of these 17 patients with 21 patients with stage IV disease and 38 suboptimally debulked patients with stage III disease treated during the same period with aggressive surgery followed by chemotherapy revealed no statistical difference in overall survival between these 17 patients and the two groups of patients. The postoperative hospital stay and complication rate were significantly lower for the 9 patients who had surgery than for the 21 patients with stage IV disease. This report suggests that in patients with presumed ovarian cancer and significant medical problems or with a priori nondebulkable tumor, initial chemotherapy and then surgery should be considered.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy.

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

Adenocarcinoma↗

PubMed1992

Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy.

PURPOSE: To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy. PATIENTS AND METHODS: For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT. RESULTS: Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria. CONCLUSIONS: Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.

Adenocarcinoma↗

PubMed1990

Treatment of hairy cell leukemia with alternating cycles of pentostatin and recombinant leukocyte A interferon: results of a phase II study.

Fifteen patients with hairy cell leukemia (HCL) were treated with deoxycoformycin (pentostatin; dCF) (4 mg/m2 intravenous [IV] every week x 3) and recombinant interferon-alpha 2a (rIFN-alpha 2a) (3 x 10(6) units subcutaneously [SC] daily x 4 weeks) in alternating months for a total of 14 months. Eleven patients had undergone splenectomy; four had received prior systemic therapy with chlorambucil and/or steroids. All 15 are evaluable for toxicity and peripheral blood response, while 14 are assessable for bone marrow response. Toxicity was tolerable with grade 3 or 4 nausea and vomiting in three patients, neutropenic fevers in five, transient but significant depression in eight, and localized cutaneous herpes zoster in four. Circulating hairy cells were undetectable by the end of the first month in 10 of 13 patients, and by the end of the second month in the other three. Fourteen patients had bilateral bone marrow biopsies performed at baseline after 6 months of treatment, at the end of treatment (14 months), and at 6-month intervals during follow-up. Before treatment, all patients had hypercellular marrows with hairy cels replacing normal marrow elements; all showed at least a 95% clearing of their hairy cell infiltrate by 6 months of therapy. However, small collections of residual hairy cells could be detected intermittently on at least one side of bilateral samples in all patients. All patients have completed treatment with a median duration of follow-up off therapy of 27 months (range, 15 to 31 months). To date, all peripheral counts and serum soluble interleukin-2 receptor (sIL2R) levels remain stable, and no patient has had progression of the hairy cell infiltrate in the bone marrow. Although no patient achieved a pathologic complete response, alternating monthly cycles of dCF and rIFN-alpha 2a produced durable partial remissions (PRs) in all patients. Continued follow-up is required to determine the length of such remissions.

Adult↗

PubMed1991

Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer.

Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

Preclinical evaluation of aclacinomycin A for the intraperitoneal treatment of human ovarian carcinoma.

Combination chemotherapy regimens have produced a pathological complete response rate of only 1%-25% in patients with advanced ovarian cancer. Patients with small-volume residual disease after treatment are refractory to further systemic therapy, and most eventually die of their disease. Intraperitoneal (i.p.) chemotherapy, particularly with adriamycin or cisplatin has shown promise in these patients. However, the dose-limiting painful peritonitis associated with i.p. adriamycin makes this regimen potentially too toxic for many patients. Aclacinomycin A, another anthracycline antibiotic, has been found to have activity against a wide variety of murine tumors and human xenografts. It has also demonstrated clinical efficacy in phase I and II trials against refractory ovarian cancer and has less pronounced vesicant properties than adriamycin, making it an ideal candidate for i.p. use in ovarian cancer patients. In vitro clonogenic assays utilizing a battery of adriamycin-sensitive and -resistant human ovarian carcinoma cell lines have shown that aclacinomycin A is more cytotoxic than adriamycin in all cell lines tested. In addition, aclacinomycin A was found to prolong survival in a nude mouse xenograft of i.p. human ovarian cancer. These results have provided the experimental rationale for an ongoing clinical trial of i.p. aclacinomycin in refractory ovarian cancer patients at the Medicine Branch, NCI.

Aclarubicin↗

PubMed1990

Chemotherapy and radiation therapy before transhiatal esophagectomy for esophageal carcinoma.

Recent efforts to improve survival in patients with esophageal carcinoma have combined both systemic and local therapy. From October 1985 to October 1987, 43 patients with local-regional esophageal cancer (adenocarcinoma in 21, squamous cell in 22) were treated with cisplatin, vinblastine, and 5-fluorouracil chemotherapy concurrent with 4,500 cGy radiation therapy for 21 days before transhiatal esophagectomy 3 weeks later. Two patients died of chemotherapy/radiation therapy toxicity. Forty-one completed preoperative chemotherapy/radiation therapy. At operation, 2 patients had incurable metastatic disease; 39 underwent transhiatal esophagectomy. Eleven patients had no residual tumor in the resected specimen for a 27% (11 of 41) pathological complete response rate. Preoperative chemotherapy/radiation therapy resulted in no increased perioperative morbidity as compared with our historical controls. One patient died postoperatively of an unrecognized brain metastasis (2% operative morbidity). At a median follow-up of 27 months, 20 patients (47%) are alive and clinically disease-free and 21 have died, 19 from progression of their carcinoma. The median survival time for all 43 patients is 29 months (Kaplan-Meier estimate), and cumulative survival is 72% at 12 months, 60% at 24 months, and 46% at 36 months. All 11 patients with a complete response are alive at a median follow-up of 36 months, and all are disease-free. The 2-year survival of 60% of this group as compared with 32% in our earlier patients treated with transhiatal esophagectomy alone suggests that intensive combined modality therapy improves survival in these patients. A randomized prospective trial is now in progress.

Adenocarcinoma↗

PubMed1987

A randomized study of cyclophosphamide and cis-platinum with or without doxorubicin in advanced ovarian carcinoma.

Two hundred sixty-seven patients with advanced epithelial ovarian carcinoma were randomized to cis-platinum and cyclophosphamide versus cis-platinum, cyclophosphamide, and doxorubicin. Complete pathological response, evaluated at second-look laparotomy and survival, showed no differences between the two treatment groups. Recurrence-free survival after negative second look was 61% at 24 months.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer.

Thirty-one ovarian cancer patients with minimal residual disease after intravenous cisplatin combination chemotherapy were treated with intraperitoneal carboplatin (IP-Ca). The dose of IP-Ca was escalated from 150 to 350 mg/m2. Twenty-two patients received at least three courses of IP-Ca and were evaluable for efficacy. Third-look laparotomy was done in 10 patients. Two patients obtained a complete pathological response (CPR) lasting 33+ and 41+ months, respectively; 8 patients had minimal residual disease. Median survival for all patients was 14+ months. All patients were eligible for toxicity. Maximum tolerable dose in these heavily pretreated patients was 300 mg/m2 IP-Ca. The dose-limiting toxicity was thrombocytopenia; in 27% of the patients who received 350 mg/m2 IP-Ca, WHO grade 4 thrombocytopenia was seen. No patient had WHO grade 4 leukopenia. Subjective side effects consisted of mild nausea and vomiting (WHO). In conclusion, IP-Ca can produce CPR in heavily pretreated patients with only minor side effects.

Adult↗

PubMed1990

Salvage whole-abdominal irradiation following chemotherapy failure in epithelial ovarian carcinoma.

During the period 1977 to 1985, 12 patients with FIGO stage II and III epithelial ovarian carcinoma failed to achieve a pathologic complete response with chemotherapy and underwent salvage whole-abdominal irradiation (WAXRT). Six of these patients had gross residual disease present at the time of irradiation, and three (50%) were unable to complete the planned radiotherapy. All eventually failed in the treatment field; their 5-year actuarial survival and local control rates were zero. The other six were irradiated without residual macroscopic disease. Five of the six (83%) were able to complete WAXRT as planned without prolonged delays. The 5-year actuarial survival and local control rates for this group were 21 and 25%, respectively. The actuarial laparotomy rate to relieve bowel obstruction following WAXRT was 40% at 2 years. The results from this and other series indicate that salvage WAXRT is not effective for patients irradiated with macroscopic tumor. However, WAXRT appears to be potentially curative for a small but significant percentage of patients irradiated without gross disease, although the risk of significant complications is high.

Abdomen↗

PubMed1991

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗

PubMed1992

Proliferating cell nuclear antigen in epithelial ovarian cancer: relation to results at second-look laparotomy and survival.

We determined the proliferative index (PI) of 92 previously untreated advanced epithelial ovarian cancers using PCNA/cyclin immunostaining and image analysis quantitation. In this retrospective study, there was a relationship between tumor PI and 5-year survival. For patients with a tumor PI greater than the median, the estimated 5-year survival was 44%; for patients with a tumor PI below the median, the estimated 5-year survival was 15% (P = 0.003). This may partly reflect sensitivity to chemotherapy, as those patients with more rapidly proliferating tumors were more likely to achieve a pathologic complete response to platinum-based therapy.

Adult↗