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Results for “Pathologic response”

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PubMed2003

Preoperative chemotherapy for esophageal cancer with paclitaxel and carboplatin: results of a phase II trial.

OBJECTIVE: Paclitaxel has one of the highest response rates when used as a single agent in patients with esophageal cancer. The combination of paclitaxel and carboplatin has been shown to be a well-tolerated and safe regimen in non-small cell lung cancer. The objective of this study was to determine the efficacy of preoperative paclitaxel and carboplatin in patients with carcinoma of the esophagus. PATIENTS AND METHODS: A phase II trial was initiated in January 1999 and concluded in January 2001. All patients had potentially resectable disease (including clinical T4 lesions). Patients with stage I disease and those with visceral metastases were excluded. All underwent preoperative computed tomography scanning and endosonography for staging. Paclitaxel (200 mg/m(2)) and carboplatin (area under the curve = 6) were given on days 1 and 22. Esophagectomy was carried out on weeks 6 to 8. RESULTS: Twenty-six (11 epidermoid, 15 adenocarcinoma) patients completed the trial. Median age was 61.5 and 85% were men. Preoperative staging showed: stage IIA, 6 patients; stage IIB, 1 patient; and stage III, 19 patients. All patients completed their preoperative chemotherapy. There was no unexpected chemotherapy-related toxicity. A major clinical response was achieved in 16 patients (61%: 19% complete, 42% partial). Resectability was 77% (20/26). A complete pathologic response was seen in 11% of all patients and in 25% of those with epidermoid cancer. Hospital mortality and morbidity were 4 and 27%, respectively. Overall 3-year survival was 48% (64% for resected patients, median not reached). All 6 unresectable patients died within 6 months of exploration. CONCLUSION: Paclitaxel-carboplatin combination is a safe and well-tolerated regimen for esophageal cancer with clinical response rates comparable to historical controls. This regimen may be especially suitable for patients with epidermoid cancer, who had a 25% pathological complete response in this report.

Adenocarcinoma↗

PubMed2001

Issues involved in research into the neoadjuvant treatment of breast cancer.

Randomized studies have failed to find convincing evidence that neo-adjuvant chemotherapy results in improved overall survival. This may be related to limited efficacy of the regimens used. A sequence of an anthracycline-based primary chemotherapy followed by docetaxel has shown promising results which are briefly discussed. The assessment of the efficacy of neoadjuvant therapy should be based on the evaluation of pathological response and a simple, reproducible method of grading differential response would be of great value. Positive identification of tumor stroma is essential in defining pathological complete response (pCR). This paper presents a grading scheme based purely on microscopic assessment which classifies patients into five groups with significantly different disease-free and overall survival. A system dividing patients into only two groups, i.e. those with pCR or those with any evidence of invasive tumor, may lose information of prognostic value. Assessing the response of metastatic disease in the lymph nodes, as well as response of the primary tumor, may further refine our ability to identify those patients likely to gain most from neoadjuvant chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract.

Cisplatin-based multiple-drug chemotherapy is currently considered the most effective treatment for advanced and metastatic urothelial cancers. We treated 15 patients with locally advanced urothelial cancers of the upper urinary tract using the cisplatin-based multiple-drug regimen in a neoadjuvant setting. The regimens administered were: M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin); MEC (methotrexate, etoposide and cisplatin), or M-VEC (methotrexate, vinblastine, epirubicin and cisplatin). Total nephroureterectomy was performed in all patients and response was evaluated pathologically Of 15 patients 2 (13%) achieved a pathological complete response, 6 (40%) a pathological partial response, for an overall response rate of 53% (95% confidence limits 29-77%). The median durations of response were 54 months for patients with a pathological complete response and 15.5 months for patients with a pathological partial response. One of six patients with a pathological partial response and 4 of 7 with no remission died of cancer. While a positive relationship between the pathological response and prognosis was observed, adequate follow-up is needed to assess the ability of neoadjuvant chemotherapy to improve the prognosis of patients with locally advanced urothelial cancer of the upper urinary tract.

Adenocarcinoma↗

PubMed2001

Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications.

PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy. METHODS: A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.

Adenocarcinoma↗

PubMed1990

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.

Adult↗

PubMed2003

Is there still a role for neoadjuvant therapy in breast cancer?

The role of neoadjuvant chemotherapy in locally advanced breast cancer is firmly established. There is now also an emerging role for neoadjuvant systemic therapy in the treatment of operable breast cancer. There is good evidence that the chances of breast conserving surgery can be increased with this approach and results of randomised studies indicate that survival is at least as good with neoadjuvant as with adjuvant chemotherapy. Similar clinical data are emerging with neoadjuvant endocrine therapy. For the future, there are important potential advantages in having an in vivo measure of chemosensitivity rather than blindly treating micrometastatic disease in the adjuvant setting. Clinical response to neoadjuvant treatment, and in particular complete pathological response, are predictors of subsequent outcome. Pathological involvement of axillary nodes following neoadjuvant therapy portends a poor prognosis. The potential for biological surrogate markers of response to predict for long-term outcome may allow individualisation of systemic treatment and the rapid assessment of new drugs in early breast cancer.

Antineoplastic Agents, Hormonal↗

PubMed2006

Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution.

BACKGROUND: We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC). PATIENTS AND METHODS: We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment. RESULTS: Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P<0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis. CONCLUSIONS: ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.

Breast Neoplasms↗

PubMed2004

Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy.

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer with a 5-year survival limited to approximately 40%. Diagnosis, based on clinical and/or pathological criteria, may be difficult. Optimal systemic neoadjuvant therapy and accurate predictors of pathological response have yet to be defined for increasing response rate and survival. Using DNA microarrrays containing approximately 8,000 genes, we profiled breast cancer samples from 81 patients, including 37 with IBC and 44 with noninflammatory breast cancer (NIBC). Global unsupervised hierarchical clustering was able to some extent to distinguish IBC and NIBC cases and revealed subclasses of IBC. Supervised analysis identified a 109-gene set the expression of which discriminated IBC from NIBC samples. This molecular signature was validated in an independent series of 26 samples, with an overall performance accuracy of 85%. Discriminator genes were associated with various cellular processes possibly related to the aggressiveness of IBC, including signal transduction, cell motility, adhesion, and angiogenesis. A similar approach, with leave-one-out cross-validation, identified an 85-gene set that divided IBC patients with significantly different pathological complete response rate (70% in one group and 0% in the other group). These results show the potential of gene expression profiling to contribute to a better understanding of IBC, and to provide new diagnostic and predictive factors for IBC, as well as for potential therapeutic targets.

Adult↗

PubMed2006

Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses.

PURPOSE: Adjuvant high-dose interferon-alfa-2b (HDI) improves disease-free and overall survival in patients with high-risk melanoma. However, its mechanism of action is largely unknown. Therefore, HDI was investigated in the neoadjuvant setting to assess clinical and pathologic responses after 4 weeks of HDI and to perform immunohistochemical evaluation of immune cell subsets and melanoma-associated antigens. PATIENTS AND METHODS: Patients with palpable regional lymph node metastases from melanoma (American Joint Committee on Cancer stage IIIB-C) underwent surgical biopsy at study entry and then received standard intravenous HDI (20 million units/m2, 5 days per week) for 4 weeks followed by complete lymphadenectomy and standard maintenance subcutaneous HDI (10 million units/m2 3 times per week) for 48 weeks. Biopsy samples were obtained before and after intravenous HDI and subjected to immunohistochemical analysis as well as routine pathologic study. RESULTS: Twenty patients were enrolled, and biopsy samples were informative for 17. Eleven patients (55%) demonstrated objective clinical response, and 3 patients (15%) had complete pathologic response. At a median follow-up of 18.5 months (range, 7 months to 50 months) 10 patients had no evidence of recurrent disease. Clinical responders had significantly greater increases in endotumoral CD11c+ and CD3+ cells and significantly greater decreases in endotumoral CD83+ cells compared with nonresponders. No changes in the expression of melanoma-associated lineage antigens, tumor cell proliferation, angiogenesis, or apoptosis were evident. CONCLUSION: Neoadjuvant HDI is highly effective for the treatment of palpable stage IIIB-C melanoma, and the findings of this study implicate an indirect immunomodulatory mechanism rather than a direct antitumor mechanism.

Adult↗

PubMed2006

A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy.

Adult↗

PubMed1997

Argon laser retinal lesions evaluated in vivo by optical coherence tomography.

PURPOSE: To assess the in vivo evolution of argon laser retinal lesions by correlating the cross-sectional structure from sequential optical coherence tomography with histopathologic sectioning. METHODS: Argon laser lesions were created in the retinas of Macaca mulatta and evaluated by cross-section optical coherence tomography, which was compared at selected time points with corresponding histopathology. RESULTS: Argon laser lesions induced an optical coherence tomography pattern of early outer retinal relative high reflectivity with subsequent surrounding relative low reflectivity that correlated well with histopathologic findings. The in vivo optical coherence tomography images of macular laser lesions clearly demonstrated differences in pathologic response by retinal layer over time. CONCLUSION: The novel sequential imaging of rapidly evolving macular lesions with optical coherence tomography provides new insight into the patterns of acute tissue response by cross-sectional layer. This sequential imaging technique will aid in our understanding of the rapid evolution of retinal pathology and response to treatment in the research and clinical setting.

Animals↗

PubMed2005

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.

Adult↗

PubMed2000

Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response.

Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P < 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P < 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification of clinically significant resistance and permit intervention with alternative non-cross-resistant therapies such as taxoids.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2026

Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series.

Background/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody-drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, it is unclear which patients retain meaningful benefit from platinum. We describe long-term outcomes and exploratory paired immune and genomic analyses in a single-centre cohort treated with dose-dense MVAC (dd-MVAC). Methods: We retrospectively identified 54 consecutive patients with MIBC treated with neoadjuvant dd-MVAC between November 2013 and November 2019. Forty-two underwent radical cystectomy and are assessable for pathologic response. Immunohistochemistry for CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, and NY-ESO-1 was evaluable in 31 baseline specimens and 22 paired specimens; paired genomic profiling was evaluable in 12 cases, with paired tumour mutational burden (TMB) in 10 by whole-exome sequencing and 7 by TSO-500. Paired analyses necessarily exclude patients achieving a pathologic complete response (pCR), who have no residual tumour, and most early progressors. Results: pCR was achieved in 11/42 operated patients (26%, 95% CI 15-41). Median follow-up was 87 months (IQR 24-104). Hydronephrosis was the only baseline factor associated with absence of pCR (p = 0.016). Within the operated cohort, pCR was associated with longer recurrence-free survival (log-rank p = 0.017), but the difference in overall survival did not reach significance (p = 0.121). NAC reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043) after correction for multiple comparisons, whereas TMB showed no significant change (TSO-500 p = 0.67; WES p = 0.86). No statistically significant association was detected between any baseline immune marker, including PD-L1, and pCR. The mutational landscape was largely concordant before and after NAC. Conclusions: This study was exploratory and was not powered to validate predictive biomarkers. In this long-term cohort, dd-MVAC was associated with measurable depletion of intratumoral immune populations in chemoresistant tumours, while paired genomic profiles remained broadly concordant. No pre-treatment biomarker identified platinum-refractory patients, but the small evaluable subsets mean these are hypothesis-generating rather than negative findings, and prospective studies with pre-specified biomarker endpoints are required.

chemoresistance↗

PubMed1997

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

BACKGROUND: [F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. METHODS: Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. RESULTS: The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. CONCLUSIONS: In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Animals↗

PubMed2006

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole.

Sixty-three postmenopausal women with large primary breast cancers were treated with neoadjuvant letrozole (2.5 mg daily) for 3 months. Tumour samples were taken at diagnosis and after 10-14 days and 3 months treatment. Immunohistochemical staining for Ki67, oestrogen receptor (ER) and progesterone receptor (PgR) was performed and related to clinical (ClinR) and pathological responses (PathR) after 3 months treatment. ClinR was observed in 48 of 63 cases (76.2%) and PathR in 47 of 62 (75.8%). Pretreatment Ki67 scores were similar in responders (R) and non-responders (NR). Highly significant Ki67 decreases occurred in all tumour subgroups at 10-14 days (P<0.005). A significant difference in Ki67 scores at 10-14 days (P<0.007) was found between PathR and PathNR but not between ClinR and ClinNR. At 3 months, decreases from pretreatment Ki67 scores were highly significant in all tumour subgroups irrespective of response status. However, whereas Ki67 scores were significantly different between pathological R and NR (P = 0.009), the corresponding comparison of ClinR status was not. Significant decreases between 10-14 days and 3 months were found only in ClinR and PathR (P = 0.02 and 0.045, respectively). Treatment significantly reduced PgR expression at 14 days and 3 months (both P<0.0001), but the level of changes was not different between response status groups. In summary, letrozole produces rapid and profound decreases in expression of Ki67 and PgR but changes do not always correlate with clinical and pathological responses.

Aged↗

PubMed1996

Determinants of response to a cisplatin-based regimen as neoadjuvant chemotherapy in stage IB-IIB invasive cervical cancer.

The response rate and the determinants of response to a cisplatin-based regimen of neodjuvant chemotherapy (NACT) in women with a histologically confirmed first-diagnosis of invasive bulky stage IB-IIB cervical cancer are analyzed. A total of 79 cases were treated with cisplatin (40 mg/m2) each 7 days for seven courses. During the first, fourth, and seventh cycles, ifosfamide (3.5 g/m2) was given by infusion for 24 hr. At the end of the seven cycles, 51 had a partial response (64.5%) and 4 a complete pathological response (5.1%). The overall 24-month cumulative survival was 80%, being 93% in responders and 43% in nonresponders (log-rank test, P < 0.05). With respect to the 66 subjects for whom pretreatment status of pelvic lymph nodes was available, complete or partial response was obtained in 35 of 42 subjects with negative pelvic lymph nodes at computed tomography, but in only 13 of 24 with positive lymph nodes. The corresponding odds ratios of response was 0.2 for women with positive status in comparison with those with negative status (95% confidence interval, 0.1-0.4). With respect to the 66 women who underwent surgery after NACT, of the 24 women with pretreatment positive lymph nodal status, 15 had positive nodes at surgery, but in 9 cases the histological analysis of nodes showed negative findings. Positive nodes at surgery were observed in 2 of the 42 subjects with negative nodes before treatment.

Adult↗

PubMed2004

The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile.

The aim of this study was to determine the chemosensitivity of infiltrating lobular breast carcinoma (ILC) in comparison with infiltrating ductal carcinoma (IDC). Between 1987 and 1995, 457 patients with invasive T2>3 cm-T4 breast carcinomas were treated with primary chemotherapy (CT), surgery, radiation therapy. Clinical response, the possibility of breast preservation, pathological response and survival were evaluated according to the histological type. In order to evaluate the biological differences between ILC and IDC patients and their implication with regard to tumour chemosensitivity, additional immunohistochemical stainings (oestrogen receptor (ER), Bcl2, p53, c-erbB-2 and Ki67) were performed on 129 pretherapeutical specimens. 38 (8.3%) ILC were diagnosed by core needle biopsy before CT. ILC was an independent predictor of a poor clinical response (P=0.02) and ineligibility for breast-conserving surgery after neoadjuvant chemotherapy (P=0.03). Histological and biological factors predicting a poor response to CT (histological grade, ER, Ki67 and p53 status) were more frequent in ILC than in IDC patients. After a median follow-up of 98 months (range: 3-166), the low chemosensitivity of ILC did not result in a survival disadvantage. Our results demonstrate that ILC achieved a lower response to CT than IDC because of their immunohistochemical profile. Preoperative CT did not allow a high rate of conservative treatment for ILC and therefore the use of neoadjuvant CT for ILC patients should be questioned.

Adult↗