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PubMed1998

Management of the clinically positive neck in organ preservation for advanced head and neck cancer.

BACKGROUND: To investigate clinicopathologic predictive criteria for the optimal management of neck metastases in patients with advanced head and neck cancers treated with combined chemoradiotherapy. METHODS: Prospective study, 48 patients. Mean length follow-up, 23 months. RESULTS: Neck stage predicted neck response to chemoradiotherapy; N3 necks showed more partial responses (P = 0.04), and N1 necks showed more complete responses (P = 0.12). Primary tumor site strongly predicted the pathologic response found on neck dissection in patients with a clinical partial response (cPR) following chemoradiotherapy. There was no difference in survival between patients with a clinical complete response (cCR) after chemoradiotherapy, and patients with a pathologic complete response (pCR) after neck dissection (P = 0.20); however, when grouped together, these patients survived longer than did patients with a pPR at neck dissection (P = 0.06). CONCLUSIONS: Clinical response to induction chemotherapy is a poor predictor of ultimate neck control. Induction chemotherapy followed by chemoradiotherapy, and planned neck dissection for patients with persistent cervical lymphadenopathy, provides good regional control.

Adult↗
PubMedDate not supplied

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Adult↗
PubMedDate not supplied

The use of concurrent chemotherapy with high-dose radiation before surgical resection in patients presenting with apical sulcus tumors.

PURPOSE: Patients presenting with apical sulcus tumors have historically been treated with preoperative radiotherapy followed by surgical resection. Since 1991, we have delivered an induction regimen consisting of combination chemotherapy and high-dose radiation in an attempt to improve tumor responses and increase survival for this patient population. PATIENTS AND MATERIALS: This retrospective analysis consisted of 23 (13 men and 10 women) consecutive patients who completed trimodality therapy. The median age was 53 years. Histologies included adenocarcinoma (nine patients), squamous cell (five patients), large cell (three patients), and undifferentiated non-small cell lung carcinoma (six patients). Pretreatment stages were T3NO (14 patients), T3N2 (two patients), T3N3 (one patient), T4NO (five patients), and T4N2 (one patient). Preoperative therapy consisted of daily radiotherapy (median dose, 59.4 Gy) delivered at 1.8 Gy/day and concurrent combination chemotherapy consisting of either two cycles of cisplatin and etoposide or weekly carboplatin and paclitaxel. Surgical resection typically included lobectomy with chest wall resection. RESULTS: All 23 patients were available for analysis of response and survival. The median follow-up was 53 months. The median number of days between completion of induction therapy and surgery was 56 days. Postoperative complications included prolonged atelectasis (two patients), pulmonary embolism (one patient), subarachnoid-pleural fistula (one patient), and deep vein thrombosis in the subclavian vein (one patient). The pathological complete response rate to induction therapy was 46% for the entire group. An additional 38% had evidence of tumor regression at the time of surgery. The 5-year disease-free and overall survivals were 36% and 49%, respectively. The median overall survival was 33 months. The median overall survival for those who achieved a pathological complete response has not been reached. Analysis of factors including age, sex, histology, differentiation, stage of disease, and radiation dose failed to identify any predictors of response or survival. CONCLUSION Concurrent chemotherapy and high-dose radiation can be safely delivered before surgery in patients presentingwith apical sulcus tumors. Our results compare favorably to other institutional series and support the further investigation of this approach in prospective trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

A prospective randomized pilot study to evaluate predictors of response in serial core biopsies to single agent neoadjuvant doxorubicin or paclitaxel for patients with locally advanced breast cancer.

INTRODUCTION: Response to neoadjuvant chemotherapy for locally advanced breast cancer can be correlated with long-term outcomes. Surrogate end-point biomarkers may be used to assess response to the treatment. Most reported studies assessed the effects of combination chemotherapy. We assessed the feasibility of obtaining serial core breast biopsies, and correlated rates of apoptosis, proliferation, and expression of related proteins at baseline, during, and after neoadjuvant single agent chemotherapy for locally advanced breast cancer with response. EXPERIMENTAL DESIGN: Women with a histologically confirmed unresected T(3) or T(4) infiltrating carcinoma of the breast were eligible. The first 20 patients received three cycles of doxorubicin 90 mg/m(2) followed by three cycles of paclitaxel 250 mg/m(2), or the reverse. Nine women received four cycles of each (doxorubicin 60 mg/m(2) and paclitaxel 175 mg/m(2)). Cycles were administered 14 days apart with filgastrim. End points included: (a). clinical and pathological response; (b). serial apoptotic [terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling] and proliferation (immunohistochemistry, IHC) rates; and (c). expression (IHC) of estrogen receptor, HER2, bcl2, and p53. RESULTS: From April 1997 to June 2001, 29 women were randomized. Twelve patients (42%) had a clinical complete response (cCR), and 16 (55%) had a clinical partial response. Five women (17%) had a pathological complete response, 7 (24%) had microscopic residual disease, and 17 (58%) had macroscopic residual disease. Higher baseline apoptosis and proliferation were associated with an improved pathological response (P = 0.006 and 0.003, respectively). Among 14 evaluable patients, apoptosis increased in women who had a cCR to the first agent but not in women without a cCR. Estrogen receptor-positive patients had a worse pathological response (P = 0.004). CONCLUSIONS: The selected regimen is efficacious. It is feasible to obtain serial core biopsies that are informative for studies of apoptosis and IHC. This clinical design can serve as a model for combining standard chemotherapy and novel agents.

Adjuvants, Immunologic↗
PubMed2003

Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?

BACKGROUND: The role of neck dissection (ND) after definitive chemoradiotherapy for squamous cell head and neck cancer is incompletely defined. We retrospectively reviewed 109 patients with N2-N3 disease treated with chemoradiotherapy to identify predictors of a clinical complete response in the neck (CCR-neck), pathologic complete response after ND (PCR-neck), and regional failure. METHOD: All patients were given 4-day continuous infusions of 5-fluorouracil (1000 mg/m2/d) and cisplatin (20 mg/m2/d) during the first and fourth weeks of either once daily (n = 68) or twice daily (n = 41) radiation therapy. ND was considered for all patients after completion of chemoradiotherapy and was performed in 32 of the 65 patients achieving a CCR-neck after chemoradiotherapy and in all 44 patients with residual clinical evidence of neck disease. CCR-neck, PCR-neck, and regional failure were then correlated with potential predictors, including T, N, largest lymph node size (<3 cm, > or =3 cm), primary tumor site, and radiation fractionation schedule. RESULTS: Achievement of a CCR-neck was predicted by N, N2 vs N3 (53 of 80 vs 12 of 29, p =.019) and by largest lymph node size, <3 cm vs > or =3 cm (19 of 25 vs 46 of 84, p =.06). Achievement of a PCR-neck could not be predicted by any clinical parameter. Regional failure occurred both in patients undergoing ND and those not dissected (5 of 76 vs 4 of 33, p =.33) and proved more likely only in the ND patients with residual positive pathology compared with those achieving a PCR-neck (5 of 25 vs 0 of 51, p <.001). Primary site was not a useful predictor of CCR-neck, PCR-neck, or regional failure. Most importantly, CCR-neck (vs <CCR-neck) did not predict either a PCR-neck (24 of 32 vs 27 of 44, p =.21) or regional failure (5 of 65 vs 4 of 44, p =.80). CONCLUSIONS: After chemoradiotherapy, clinical parameters do not identify those patients with residual neck node disease or those at risk for regional failure, suggesting that ND be considered for all N2-N3 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy.

Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p2lWaf1, p27KiP1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.

Adult↗
PubMed1994

[Neoadjuvant chemotherapy of invasive bladder cancer].

Neoadjuvant chemotherapy is defined as cytotoxic treatment of an invasive carcinoma of the bladder. It is primarily suitable for a curative cystectomy with the aim of improving the therapeutic chances of the definitive treatment (i.e., cystectomy, radiotherapy) by devitalization of the primary tumor and effective control of micrometastases. Thus, one of the major goals is preoperative sterilization of the tumor (stage pT0) to avoid tumor cell seeding during surgery. Until now, the documented pathological complete response rate (CRp) after 2-4 cycles of polychemotherapy has ranged from 19 to 38% plus 3 to 23% of complete surgical response (CRs) with residual superficial bladder tumors in the cystectomy specimen. The survival rates following neoadjuvant polychemotherapy differ considerably between 54 and 82% independent of the definitive treatment (cystectomy, radiotherapy). However, the response to chemotherapy has a significant impact on survival: patients with major pathological response (CRp + CRs) yielded a 75-100% disease-free survival after 4 to 5 years in contrast to 20-22% for partial or non-responders. Future studies should investigate methods predicting the outcome of polychemotherapy (i.e., identifying mdr-chemoresistant tumors by detection of P170 glycoprotein in the TUR specimen) or improving the reliability of preoperative diagnosis (clinical = pathological complete response).

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy.

PURPOSE: The relevance of apoptosis to breast cancer response to chemotherapy is unclear. We investigated whether changes in tumor cell apoptosis and Bcl-2 expression immediately after chemotherapy correlated with response to breast cancer treatment. PATIENTS AND METHODS: Serial core biopsies of 25 breast cancer primary tumors were performed at either two or three time points: before treatment (N = 24) and approximately 24 hours (N = 22) and/or 48 hours (N = 19) after the initiation of the first cycle of chemotherapy. Apoptosis levels were quantified by use of a fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) stain, and Bcl-2 and Bax were measured by semiquantitative immunohistochemical assays. All calculated P values were two sided. RESULTS: The apoptosis level at 48 hours was significantly higher in the tumors with pathological complete response or < 1 cm of residual disease (median, 22%; range, 6%-51%) than in the tumors with > 1 cm residual disease (median, 7%; range, 1%-36%); Mann-Whitney test. This difference was also present in the subgroup of 16 tumors treated with docetaxel/doxorubicin chemotherapy (25% vs 4%, respectively). A decrease in Bcl2 expression after chemotherapy relative to the expression from the pretreatment sample also correlated with disease response. Specifically, three of the nine tumors with a decrease in Bcl-2 had a pathological complete response, compared with 0 of the 15 tumors with stable levels of Bcl-2 (Fisher's exact test). There was no relationship between serial measurements of Bax and response. DISCUSSION: These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy and that the level of treatment-induced apoptosis may have some value as a predictive marker.

Adult↗
PubMed1997

Clinical and pathological response to primary chemotherapy in operable breast cancer.

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).

Adult↗
PubMed2002

Irinotecan, cisplatin, and radiation in esophageal cancer.

The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers. In phase II evaluation of weekly irinotecan plus cisplatin, response rates have exceeded 30% in esophageal and gastric cancers. Irinotecan is an active radiosensitizer in preclinical studies and clinical trials in lung cancer. We performed a phase I trial of weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Induction chemotherapy with irinotecan and cisplatin was given prior to radiotherapy, over 6 weeks, cycled on a 2-week-on, 1-week-off schedule to relieve dysphagia. Radiotherapy was given subsequently in 180-cGy daily fractions to a total dose of 5,040 cGy. Doses of chemotherapy, when given with concurrent radiotherapy, were cisplatin at 30 mg/m2 followed by irinotecan at escalated doses (40, 50, 65, and 80 mg/m2), on days 1, 8, 22, and 29. Among 18 patients entered in the trial, minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea. Hematologic toxicity has been minimal. Dose-limiting toxicity (ie, requiring more than a 2-week delay in radiotherapy) has been seen in one of three patients at the 80-mg/M2 irinotecan dose level, and accrual continues at this dose level. Among 13 evaluable patients, five complete responses have been seen (38%), including three pathologic complete responses in 10 patients undergoing surgery (30%). Asymptomatic pulmonary emboli were noted on the posttreatment computed tomography scan in 3 of 15 patients, prompting the addition of warfarin sodium (Coumadin) prophylaxis on protocol. Full doses of weekly irinotecan (65 mg/ m2) and cisplatin (30 mg/m2) can be combined safely with concurrent radiotherapy in patients with locally advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study.

PURPOSE: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. PATIENTS AND METHODS: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.

Adult↗
PubMed1995

Phase II study of intraperitoneal cisplatin plus systemic etoposide as second-line treatment in patients with small volume residual ovarian cancer.

The efficacy and toxicity of intraperitoneal (i.p.) cisplatin plus systemic etoposide were studied in 36 patients with small (< 2 cm) residual i.p. ovarian cancer after achieving a partial response to platinum-based, first-line chemotherapy. Treatment comprised 90 mg/m2 i.p. cisplatin with intravenous (i.v.) sodium thiosulphate (day 1) and 600-800 mg/m2 i.v. etoposide (days 1 and 2), every 4 weeks for four to six cycles. 7 patients achieved a pathological complete response (pCR), one a pathological partial response and 16 were clinically stable without evidence of disease. After a median follow-up of 13 months, the median progression-free survival (PFS) was 11 months (95% confidence interval 7-16 months). The actuarial PFS at 24 months is 22% (95% confidence interval 8-36%). Three of six relapses after achieving a pCR (50%) were sited i.p., and 9 of 14 other patients with disease progression (64%) had an i.p. relapse, indicating insufficient local efficacy. There was no renal toxicity, but grade 3-4 leucopenia occurred in 63% and grade 3-4 thrombocytopenia in 8% of cycles, while nausea, vomiting and complete alopecia were common. Although side-effects were acceptable, the efficacy of treatment with i.p. cisplatin plus i.v. etoposide is limited.

Administration, Topical↗
PubMed2002

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer.

PURPOSE: To determine the dose-response relationship between the probability of tumor control on the basis of pathologic tumor response (pTCP) and the residual metabolic rate of glucose (MRglc) in response to preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer and to define the level of residual MRglc that corresponds to pTCP 50% and pTCP > or = 95%. METHODS AND MATERIALS: Quantitative dynamic 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography was performed to measure regional MRglc at the primary lesion before and 2 weeks after preoperative chemoradiotherapy in an initial group of 13 patients with locally advanced NSCLC. A simplified kinetic method was developed subsequently from the initial dynamic study and used in the subsequent 16 patients. The preoperative radiotherapy programs consisted of (1) a split course of 42 Gy in 28 fractions within a period of 28 days using a twice-daily treatment schedule for Stage IIIA(N2) NSCLC (n = 18) and (2) standard once-daily radiation schedule of 45-63 Gy in 25-35 fractions during a 5-7-week period (n = 11). The preoperative chemotherapy regimens included two cycles of cisplatin, vinblastine, and 5-fluorouracil (n = 24), cisplatin and etoposide (n = 2), and cisplatin, Taxol, and 5-fluorouracil (n = 3). Patients free of tumor progression after preoperative chemoradiotherapy underwent surgery. The degree of residual MRglc measured 2 weeks after preoperative chemoradiotherapy and 2 weeks before surgery was correlated with the pathologic tumor response. The relationship between MRglc and pTCP was modeled using logistic regression. RESULTS: Of 32 patients entered into the study, 29 (16 men and 13 women; 30 lesions) were evaluated for the correlation between residual MRglc and pathologic tumor response. Three patients did not participate in the second study because of a steady decline in general condition. The median age was 60 years (range 42-78). One of the 29 patients had two separate lesions, and MRglc was measured in each separately. The tumor histologic types included squamous cell carcinoma (n = 9), adenocarcinoma (n = 13), large cell carcinoma (n = 6), and poorly differentiated carcinoma (n = 2). The extent of the primary and nodal disease was as follows: Stage IIB (T3N0M0), Pancoast tumor (n = 2); Stage IIIA, T2-T3N2M0 (n = 18); Stage IIIB: T1-T3N3M0 (n = 5) and T4N0M0 (n = 2); a second lesion, T1 (n = 1); and localized stump recurrence (n = 2). A pathologically complete response was obtained in 14 (47%) of the 30 lesions. The remaining 16 lesions had residual cancer. The mean baseline value of the maximal MRglc was 0.333 +/- 0.087 micromol/min/g (n = 16), and it was reduced to 0.0957 +/- 0.059 micromol/min/g 2 weeks after chemoradiotherapy (p = 0.011). The correlation between residual MRglc and pTCP was made using an increment value of 0.02 micromol/min/g between the maximal and minimal values of MRglc. A pathologically complete response was obtained in 6 of 6 patients with residual MRglc of < or = 0.050 micromol/min/g, 3 of 4 with < or = 0.070, 4 of 7 with < or = 0.090, 0 of 4 with < or = 0.110, 1 of 3 with < or = 0.130, and 0 of 6 with > or = 0.130 micromol/min/g. The fitted logistic model showed that residual MRglc corresponding to pTCP 50% and pTCP > or = 95% was 0.076 and < or = 0.040 micromol/min/g, respectively. CONCLUSION: The correlation between the gradient of residual MRglc after chemoradiotherapy and pTCP is an inverse dose-response relationship. Residual MRglc of 0.076 and < or = 0.040 micromol/min/g, representing pTCP 50% and pTCP > or = 95%, respectively, may be useful surrogate markers for the tumor response to radiotherapy or chemoradiotherapy in lung cancer.

Adult↗
PubMed1997

Angiographic response of locally advanced soft-tissue sarcoma following hyperthermic isolated limb perfusion with tumor necrosis factor.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is associated with a dramatic anti-tumor effect in which the neo-vascularization of the tumor is supposed to be the major target. The aim of the present study was to correlate the angiographic findings with the pathological response in patients undergoing HILP for locally advanced soft-tissue sarcoma. PATIENTS AND METHODS: Twenty-five patients, 14 male and 11 female, mean age 47 years (range 18-80) were studied. Angiographies were performed before and a median period of 7 weeks (range 4-14 weeks) after HILP. Eight weeks after perfusion, the residual tumor mass was resected and pathologically examined. The changes in tumor vascularization after treatment were scored and compared with the pathological response. RESULTS: All baseline angiograms showed a hypervascular tumor. After HILP, a normal angiography result (NA) was observed in 18 patients (72%) and an abnormal angiography result (AA) was observed in seven patients (28%). All patients with an NA showed a pathologically complete response (pCR) or a pathological partial response with > 90% necrosis of the tumor. Of seven patients with an AA, pathological examination showed a pCR in one patient, 10-50% viable tumor volume in four patients, and no pathological response after perfusion in two patients. A good correlation was seen between angiographic and pathological classification (p < 0.001). CONCLUSION: An angiography performed after hyperthermic isolated limb perfusion with TNF-alpha and melphalan provides a good indication, regardless of whether a good pathological response is expected.

Adolescent↗
PubMedDate not supplied

Role of Magnetic Resonance Imaging in the prediction of tumor response in patients with locally advanced breast cancer receiving neoadjuvant chemo-therapy.

PURPOSE: To evaluate if dynamic contrast enhanced magnetic resonance can predict the tumoural response in patients with breast cancer undergoing neoadjuvant chemotherapy. MATERIALS AND METHODS: Twenty-six patients with biopsy-proven locally advanced breast cancer underwent taxane-based neoadjuvant chemotherapy followed by radical surgery. MRI evaluations were carried out at baseline, after two of the four planned cycles of chemotherapy, and before surgical treatment. MR images, obtained with 1.5 T scanner and using dedicated surface multichannel coil (GEMS), were acquired by 3D SPGR sequences on the coronal plane before and after intravenous administration of gadolinium chelate by an automatic injector. The percent reduction of the early contrast uptake between the baseline and the second MRI was then calculated for every lesion and correlated with the outcome of interest (pCR). RESULTS: At baseline, we identified 26 lesions and two patterns of MRI enhancement: homogeneous (group 1, 14 patients) and peripheral ring-like (group 2, 12 patients). At surgery, pathological complete response was observed in 4 patients (2 patients group 1, 2 patients group 2). In group 1, the 2 cases of pCR showed a gs;70% reduction in the early contrast uptake between baseline examination and after two cycles of chemotherapy, whereas values <70% were seen in 12 cases of partial response (p=0.02). In group 2, the 2 cases of pCR showed a gs; 40% reduction in the early contrast uptake whereas all of the 10 cases of partial response had <40% reduction (p=0.02). CONCLUSIONS: In our series, the percent reduction in the early contrast uptake after two cycles of neoadjuvant chemotherapy was predictive of the achievement of a pathological complete response. However, we identified two distinct morphologic patterns associated with different cut-offs in the predictive value of the early contrast uptake reduction between baseline and intermediate examination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Phase II trial of high-dose cisplatin plus ifosfamide as first-line followed by carboplatin as second-line treatment in epithelial ovarian carcinoma.

BACKGROUND: In a previous study of combined platinum and ifosfamide we found a pathologic complete response rate of 42%. The present study was to test whether the high response rate could be reproduced or even improved by combining high-dose cis-platinum and increased dose of ifosfamide. METHODS: Forty-two previously untreated ovarian cancer patients were included in the study. Cisplatin 50 mg/m2 and ifosfamide 2000 mg/m2 together with mesna 1200 mg/m2 were given daily, Day 1-3 every 4 weeks for six cycles, followed by second-look laparotomy. In the event of residual disease carboplatin was given every 4 weeks for a further six cycles. RESULTS: The pathologic complete response rate was 20% (8 of 41). Five of 26 patients achieved a further response on carboplatin. Hematologic and nonhematologic toxicity caused dose reduction in more than 90 and 50% of the patients, respectively. CONCLUSION: The results of this high-dose regimen equals those obtained with conventional, far less toxic, regimens. Only patients with potentially platinum-sensitive tumors achieved further response when crossed over to the analogue, which may indicate that prolonged treatment is better than increased dose. A randomized trial is still needed to assess the importance of dose intensity in ovarian cancer.

Adult↗
PubMed1997

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Adenocarcinoma↗
PubMed2003

Multimodality treatment for esophageal cancer: the role of surgery and neoadjuvant therapy.

Treatment of esophageal cancer has traditionally included surgery as the initial modality. Neoadjuvant chemoradiation therapy has been introduced with the goal of downstaging tumors before surgical resection; however, its role in esophageal cancer remains controversial. We report 116 patients who underwent esophagogastrectomy with reconstruction for carcinoma of the esophagus or esophagogastric junction over a 10-year period (January 1, 1990 to June 1, 2001). Forty patients underwent neoadjuvant radiation and chemotherapy followed by surgery. Hospital mortality in this group was 7.5 per cent, complete pathologic response (CPR) was 37.5 per cent, and overall 3- and 5-year survival rates were 47 and 38 per cent. Five-year survival in the 15 patients with CPR was 85 per cent. Five patients underwent neoadjuvant single-agent therapy (four chemotherapy and one radiation) followed by surgery, and none survived to 3 years. Seventy-one patients underwent surgery without neoadjuvant therapy. Hospital mortality in this group was 1.4 per cent, with 3- and 5-year survival of 21 and 17 per cent--a decreased long-term survival compared with the neoadjuvant therapy group despite the observation that patients who underwent neoadjuvant therapy had a larger tumor size on presentation (5.5 +/- 0.4 cm vs 3.8 +/- 0.2 cm; P = 0.002). Squamous cell carcinomas seemed to be more responsive to neoadjuvant radiation and chemotherapy followed by surgery than were adenocarcinomas, with a CPR of 44.4 versus 35.5 per cent; however, 5-year survival rates in these complete responders were not significantly different (100% and 78%, respectively; P = 0.97). We report that esophagogastrectomy in conjunction with neoadjuvant therapy results in increased survival compared with surgery without neoadjuvant therapy (P < 0.01), although there may be an increased perioperative mortality associated with neoadjuvant therapy. Further studies are needed to evaluate the role of preoperative chemoradiation and to better identify the pretreatment characteristics of patients with a complete pathological response.

Adenocarcinoma↗