Differences In Failure Patterns Research Articles

Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: Long-term results of a randomized controlled trial

BackgroundThis is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.MethodsThis trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.ResultsThere were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.ConclusionsPreoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC.

Differences in Patterns of Failure in Patients Treated With Accelerated Partial Breast Irradiation Versus Whole-Breast Irradiation: A Matched-Pair Analysis With 10-Year Follow-Up

To examine 10-year results of a single institution's experience with radiotherapy limited to the region of the tumor bed (i.e., accelerated partial breast irradiation, [APBI]) in selected patients treated with breast-conserving therapy (BCT) and compare them with results of matched BCT patients who underwent whole-breast irradiation (WBI). A total of 199 patients with early-stage breast cancer were treated prospectively with BCT and APBI using interstitial brachytherapy. To compare potential differences in local recurrence rates on the basis of the volume of breast tissue irradiated, patients in the APBI group were matched with 199 patients treated with WBI. Match criteria included tumor size, nodal status, age at diagnosis, margins of excision, estrogen receptor status, and use of adjuvant tamoxifen therapy. Local-regional control, disease-free survival, and overall survival were analyzed between treatment groups. Median follow-up for surviving patients was 9.6 years (range, 0.3-13.6 years). Eight ipsilateral breast tumor recurrences (IBTRs) were observed in patients treated with APBI. The cumulative incidence of IBTR at 10 years was 5%. On matched-pair analysis, the rate of IBTR was not statistically significantly different between the patient groups (4%, 95% confidence interval [CI] 1.3-6.7% for WBI therapy patients vs. 5%, 95% CI 1.5-8.5% for APBI patients; p = 0.48). Radiation therapy limited to the region of the tumor bed (APBI) produced 10-year local control rates comparable to those from WBI in selected low-risk patients.

Detonation diffraction in gases

We have experimentally investigated detonation diffraction out of a round tube into an unconfined half-space. The focus of our study is examining how the extent of detonation cellular instability influences the quantitative and qualitative features of diffraction. Detailed quantitative and qualitative measurements were obtained through simultaneous schlieren imaging, multiple-exposure chemiluminescence imaging, and planar laser-induced fluorescence imaging of OH molecules. Two types of stoichiometric mixtures, highly diluted H 2–O 2–Ar and H 2–N 2O, were studied in the sub-critical, critical and super-critical regime. These mixture types represent extreme cases in the classification of cellular instability with highly diluted H 2–O 2–Ar mixtures having very regular instability structures and H 2–N 2O having very irregular instability structures. The most striking differences between the mixtures occur in the sub-critical and critical regimes, for which the detonation fails to transition into the unconfined half-space. For the H 2–O 2–Ar mixture, the velocity on the center line was found to decay significantly slower than for the H 2–N 2O mixture. In case of the H 2–O 2–Ar mixture, it was evident from simultaneous schlieren-fluorescence images that the reaction front was coupled to the lead shock front up to 2.3 tube diameters from the exit plane. For the H 2–N 2O mixture, the reaction front velocity decreased to 60% of the corresponding Chapman–Jouguet value at 1.1 tube diameters from the tube exit plane. A geometric acoustic model showed that the observed differences in failure patterns are not caused by the differences in thermodynamic properties of the two mixtures but is linked to the larger effective activation energy and critical decay time in the H 2–N 2O mixture as compared to the H 2–O 2–Ar mixture. The re-initiation events appear similar for the two mixtures and are a consequence of local fluctuations at random locations within the region between the lead shock and decoupled reaction zone, resulting in strong transverse detonations sweeping through shocked but largely unreacted gas.

The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy

Purpose: To investigate the prognostic significance of the pre- and posttreatment serum squamous cell carcinoma antigen (SCC) levels in patients with Stage I-IVA squamous cell carcinoma of the cervix primarily treated by radiotherapy. Materials and Methods: 401 patients with squamous cell carcinoma of cervix primarily treated with radiotherapy (RT) were included in this study. All had preRT, and 249 patients had postRT serum SCC values. The association of pretreatment SCC level with the clinical parameters, including stage, hemoglobin (Hb) level, age, cell differentiation, and lymph node status, was assessed by univariate and multivariate analysis. The prognostic significance of pretreatment SCC level and these clinical parameters were evaluated. The impact of postRT residual induration and SCC levels on survival was analyzed. Results: 1. PreRT SCC level strongly correlated with stage. After controlling for stage, only SCC levels higher than 10 ng/ml were associated with enlarged lymph nodes shown in CT scan. No association of preRT SCC level with other clinical parameters was found. 2. SCC level higher than 10 ng/ml, but not between 2–10 ng/ml, had significant impact on survival in a multivariate analysis. Stage, Hb levels (<10 g/dl) and positive lymph node shown by CT scan were also independent prognostic factors for survival. No significant difference in failure pattern in terms of local and/or distant sites was found in patients with different SCC levels. 3. Patients with residual induration and/or persistently elevated SCC level at 2–3 months after RT had a significantly higher incidence of treatment failure. Persistently elevated SCC level is a stronger predictor for treatment failure than residual induration by pelvic examination, and is associated with a higher incidence of distant metastasis. One third of patients with initial SCC level higher than 10 ng/ml had persistently elevated SCC. Conclusion: Pretreatment SCC levels higher than 10 ng/ml are an independent predictor for poor prognosis in patients included in this study, and can be used as one of the prognostic factors for selection of patients for intensive treatment. Persistently elevated SCC levels after RT is a strong predictor for treatment failure. A combination of clinical pelvic examination and SCC levels provides useful information for the need of further work-up and management.

Age-Related Prostate Cancer Metastases

Objectives. Metastatic prostate cancer results in significant patient morbidity, health care expenditure, and ultimately in mortality. We sought to identify patient and treatment factors predictive of distant metastases in patients completing external beam radiotherapy. Methods. Five hundred sixty-seven patients completing external beam radiotherapy at Fox Chase Cancer Center, Philadelphia, Pennsylvania between March 1987 and November 1994 for Stage T1 to T3 tumors were analyzed. Distant metastases were detected by radionuclide bone scans. Estimates of rates for distant metastases as a first failure were conducted using cumulative incidence methods and predictors of failure were analyzed univariately and multivariately. Results. The median follow-up was 46 months. On univariate analysis, the following were statistically significant predictors of distant metastases at 5 years: patient age greater than 65 years, pretreatment prostate-specific antigen (PSA) level, advanced stage, lower radiation dose, and Gleason score 7 to 10. Multivariate testing confirmed that age greater than 65 years, high pretreatment PSA level, lower radiation dose, and advanced stage were significant independent predictors of distant metastases. Conclusions. Men over the age of 65 years are more likely to experience distant failure than are younger men. The discovery of age-related differences in patterns of failure has significant therapeutic implications with regard to patient selection, trial design, and adjuvant therapy recommendations. Furthermore, age-related differences in failure may influence comparison of outcome data for radiotherapy series, which tend to have older patients, to surgical reports that usually include significantly younger men.

High-Dose Conformal Radiotherapy Influenced the Pattern of Failure But Did Not Improve Survival in Glioblastoma Multiforme

Background and Purpose: Although glioblastoma multiforme is clearly radiation-resistant, there is evidence of a dose–dependent response relationship. The purpose of the study was to evaluate the impact of higher dose by rotational multileaf collimator (MLC) conformal radiation therapy. Materials and Methods: From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme were treated using the rotational MLC conformal therapy. There were 25 men and 13 women with a median age of 47 years (12–73 years, mean 46.5 years). Median Karnofsky performance score was 80 (30–100, mean 78.2). Median tumor volume was 64 cc (8–800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy in 1, partial resection in 13, subtotal resection in 21, and gross total resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy) in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter. Biweekly i.v. chemotherapy was also administered for both arms. Results: The 1-year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and 15%, respectively. Univariate analysis showed the initial tumor volume, residual tumor volume, and Karnofsky performance score were statistically significant factors for survival. Only the residual tumor volume was statistically significant by multivariate analysis. The 5-year survival rate of patients with residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90-Gy Group appeared inferior to that of the Low-Dose Group, though no statistical difference was seen (the 3-year survival was 40% vs. 22%). Local failure was observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in pattern of failure was statistically significant. Two patients of the High-Dose Group developed radiation necrosis and one died of it. Conclusions: The high-dose conformal radiotherapy did not improve survival in the disease, but did change the pattern of failure.

Failure patterns of four osseointegrated oral implant systems.

The aim of this metanalysis was to investigate possible differences in failure patterns among four different osseointegrated oral implant systems. Only systems with a supposed scientific validation, based on long-term follow-up studies, were selected for this analysis, i.e. the Brånemark system, the Calcitek Integral system, the Interpore IMZ system and the Straumann ITI system. While several prospective reports could be found on the Brånemark system, only a few retrospective investigations concerning the ITI and the IMZ systems were available. No data on the Integral system could be employed. Despite these limitations, a substantial difference in failure patterns among various implant systems was observed. The Brånemark implants showed a higher incidence of early failures, though sharply decreasing over time. On the contrary, IMZ implant characterized by rougher surfaces displayed a lower incidence of early failures, but showed constant or increased failure rates over time. For the ITI implants, for example, a higher prevalence of late failures, attributable to chronic bacterial infection (peri-implantitis), was observed when compared to the Brånemark system. With the exception of the latter implant system, prospective long-term follow-up studies, using similar and well-defined success criteria, are needed for the others to confirm the current preliminary findings.

2072 Difference in pattern of failure between moderate dose conventional and high dose conformal techniques for postoperative radiotherapy of glioblastoma multiforme

2072 Difference in pattern of failure between moderate dose conventional and high dose conformal techniques for postoperative radiotherapy of glioblastoma multiforme

The role of radiotherapy in the treatment of subtotally resected benign meningiomas.

Thirty-six patients with benign meningioma were treated for primary or recurrent disease by subtotal resection and external beam irradiation from 1968-1986 at Massachusetts General Hospital. Comparison is made with 79 patients treated by subtotal surgery alone from 1962-1980. Progression-free survival for 17 patients irradiated after initial incomplete surgery was 88% at 8 years compared with 48% for similar patients treated by surgery alone (p = 0.057). 16 patients incompletely resected at time of first recurrence were irradiated and 78% were progression-free at 8 years while 11% of a similar group treated by surgery alone were progression free (p = 0.001). Long term overall survival was high and similar in both control and study groups. Two patients were irradiated at second recurrence and 1 patient at third recurrence. Twenty-five patients were treated with photons alone and have a median follow-up of 57 months, 6 patients have recurred at doses 45-60 Gy. Eleven patients were treated with combined 10 MV photons and 160 MV protons utilizing 3-D treatment planning. These patients have been followed for a median of 53 months and none have failed to date. Eight of 11 received 54-60.4 Gy and 3/11 greater than 64.48 Gy. Sex, age, pathology grade and score, surgery and timing of radiation therapy were not associated with significant differences in failure patterns within the irradiated study group (p less than 0.1). Complications have been seen in 6 irradiated patients.

Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG

A total of 285 patients with medically inoperable (RTOG Stage T1–2, NO-1) or unresectable (RTOG Stage T3, NO-1) non-small cell carcinoma of the lung were randomized by the Radiation Therapy Oncology Group (RTOG) to receive radiation therapy (6000 cGy total dose/6 weeks) plus levamisole (2.5 mg/kg twice weekly for 2 years or until tumor progression) or a placebo. One hundred twenty-nine evaluable patients were assigned to placebo and 131 to levamisole. This report is based on 260 (91 %) eligible patients who started treatment and have adequate follow-up. Fifty percent of the patients in both treatment groups had Karnofsky scores of 90–100; 72% had squamous cell carcinoma, 12% adenocarcinoma, and 16% large cell undifferentiated carcinoma; 60% had RTOG Stage I or II primary tumors and 40% had Stage III (T3, N0–1) tumors. Complete regression of tumor was reported in 20% of the patients treated with levamisole and 36% of those receiving placebo. An additional 33% and 19%, respectively, had a partial response (trend test p = 0.08). Median survival was 9 months for patients treated with levamisole and 12 months for those on placebo (two-sided p < 0.01); at 2 years, patients treated with levamisole had a 15% survival rate as compared to 24% in those receiving placebo. The cumulative proportion failing within the irradiated field with or without other sites of progression at 2 years was 30% in the levamisole group and 34% in the placebo patients. Median progression-free survival was 6 months for patients on levamisole and 7 months for those on placebo (overall two-sided p = 0.014); the estimated proportions progression-free at 2 years were 11% and 18%, respectively. The study showed no significant prolongation of survival, progression-free survival, or differences in patterns of failure in irradiated patients treated with levamisole compared with a placebo. Toxicity related to this immunoadjuvant was, in general, of moderate clinical importance. This study confirms a report by the Southeastern Cancer Study Group concluding that levamisole combined with definitive irradiation has no benefit in the treatment of unresectable non-small cell carcinoma of the lung.

Phase I–II study of prophylactic hepatic irradiation with local irradiation and systemic chemotherapy for adenocarcinoma of the pancreas

Although the addition of 5-FU to radiation therapy for locally advanced adenocarcinoma of the pancreas improved short-term survival (GITSG), there were no differences in patterns of failure. Hepatic metastases were equally common in both groups. Therefore, a pilot study of prophylactic hepatic irradiation was developed. Between March 1983 and May 1985, 16 patients were entered in a Phase I/II study of prophylactic hepatic irradiation with local irradiation and systemic chemotherapy for adenocarcinoma of the pancreas at the Medical College of Wisconsin Affiliated Hospitals. Megavoltage radiation (1.8 Gy/fraction) was given to the pancreas with a minimal margin (2 cm) around the tumor, localized by surgical clips or CT scan with a total dose of 61.2 Gy over 7 weeks. Prophylactic hepatic irradiation was added to the fourth week of irradiation to a total dose of 23.4 Gy over 2 1 2 weeks. 5-Fluorouracil, 500 mg/M2/day was given at Day 1, 2, 3, 29, 30, and 31 of radiotherapy, then a weekly maintenance for I year. Fifteen patients were evaluable: One patient refused chemotherapy. The follow-up period was 14 to 50 months (median 26 months). The most common side effect was nausea. Maintenance 5-FU was discontinued in one patient because of GI bleeding. Three-quarters of the patients developed temporary elevations of hepatic enzymes. No severe or life-threatening complications were observed. One, 2-, 3-, and 4-year disease-free survivals are 66.7%, 46.7%, 20% and 13.3%, respectively. Patterns of failure revealed that only two patients had hepatic metastasis as the first site of failure, five patients died of abdominal carcinomatosis, and three patients failed in the pancreas. Two patients died without evidence of cancer. Two patients are alive and well beyond 4 years after the diagnosis. This study confirms that such aggressive combined modality treatment is well tolerated and suggests that the frequency of hepatic metastasis can be reduced.

Potentially curative surgery of colon cancer: patterns of failure and survival.

In an effort to determine the patterns of failure and survival of colon cancer, a retrospective review of 294 patients who underwent potentially curative surgery at the New England Deaconess Hospital (NEDH) was performed. For the entire group, the 5-year crude survival rate was 68% and the actuarial rate was 80%. Survival decreased with increasing bowel wall penetration by tumor and the presence of lymph node metastasis. Although survival varied with the tumor site, none of the differences was statistically significant. Other variables, including the grade of adenocarcinoma, size, and the type of surgery had a significant impact on survival. Patterns of failure, expressed as the actuarial incidence of first diagnosed failure at 5 years, were examined by stage and site. There was a trend toward increased failure with increasing bowel wall penetration by tumor and the presence of lymph node metastasis. Abdominal failure, either as the only site or as a component of failure, was the most common type of failure. When compared by site, patients with cecal carcinoma had a significantly lower incidence of local and distant failure than patients with disease in other selected sites. No differences in patterns of failure were seen in patients with carcinomas in the mobile sections of the colon compared with those who had disease arising in the nonmobile sections of the colon. These data may be useful in identifying those patients who might benefit most from adjuvant therapy.