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The effect of delaying radiation therapy for systemic chemotherapy on local-regional control in breast cancer.

BACKGROUND: It remains controversial as to whether the administration of chemotherapy prior to radiation following the surgical treatment for localized breast cancer compromises local control. METHODS: The outcome of 290 patients who received chemotherapy prior to breast or chest wall irradiation following curative breast cancer surgery was retrospectively analyzed to determine if delaying radiation from the time of surgery adversely affects local-regional control. The patients were divided into three groups according to the time interval from definitive surgery to the start of radiation: group 1, < 5 months; group 2, 5 to < 7 months, and group 3, 7+ months. Local-regional and distant failure events were analyzed according to the time delay from surgery to radiation. RESULTS: The median follow-up was 6.0 years (range, 7 months to 15 years). Loco-regional failure was observed in 22 patients, 18 of which occurred within the original radiation fields. There was no significant adverse effect on local control or distant failure from delaying radiation for systemic chemotherapy. Univariate and multivariate analyses revealed that positive margins after surgery were associated with increased local recurrence. CONCLUSION: Delaying radiation therapy for greater than 7 months, in order to administer chemotherapy following curative breast cancer surgery, does not compromise local control. However, positive margins were significantly associated with higher rates of local failure and even an increase in radiation boost dose was not able to fully counteract the increased risk of local failure.

Antineoplastic Combined Chemotherapy Protocols↗

Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control.

In a series of 1623 men with a follow-up of 5 +/- 3 years (range 1-13) after anatomic RRP for clinically localized prostate cancer, 17% (276/1623) have shown recurrence. A detectable PSA was the only evidence of recurrence in 7.9%, whereas 2.5% have recurred locally and 5.4% have developed distant metastases. The overall actuarial progression-free rate for these men at 10 years was 68%. Actuarial rates at 10 years were 18% for development of an isolated PSA recurrence, 8% for local recurrence, and 9% for distant recurrence. The actuarial likelihood of a postoperative recurrence increased with increasing clinical stage, Gleason score, preoperative PSA level, and pathologic stage. Although not shown in our previous report, the actuarial rate of recurrence of tumors with a Gleason score of 7 was statistically different from that of tumors of higher Gleason score (8-10). As well, men with preoperative PSA levels of 10.1 to 20 ng/mL experienced recurrence at a significantly lower rate than did men with preoperative PSA levels greater than 20 ng/mL. By using a combination of Gleason score, pathologic stage, and surgical margin status, we demonstrated that the presence of a positive surgical margin did not dramatically affect recurrence in tumors of Gleason scores 2 to 6 with capsular penetration. Surgical margin status was important in high-grade tumors with capsular penetration. In fact, tumors with capsular penetration, Gleason score of at least 7, and a positive surgical margin behaved similarly to tumors with invasion of the seminal vesicles. Preservation of potency did not adversely influence cancer control. The Gleason score, presence or absence of seminal vesicle or lymph node involvement, and the timing of PSA recurrence are all important variables in predicting eventual local versus distant failure associated with an isolated rise in serum PSA. Overall actuarial cause-specific survival at 5 and 10 years was 99% and 93%. Although there was no difference in survival among men grouped by TNM stage or preoperative PSA, advancing histologic grade and pathologic stage did have an effect on actuarial cause-specific survival. Men undergoing RRP for clinically localized prostate cancer showed a 16% actuarial rate of development of metastatic disease at 10 years. This is considerably better than conservative therapy and justifies RRP as the treatment of choice for men with clinically localized disease who are otherwise healthy and have a greater than 10-year life expectancy.

Disease Progression↗

[Importance of local control of cancer after conservative therapy].

The role of local control in the cure of solid tumors remains a matter of crucial importance particularly for the cases of conservative therapy. Arguments that higher local control rates would result in more cured patients is a subject of controversies for some tumors as breast cancer. For tumors with different natural history, the authors outlined the crucial role of local control to improve cure rate thank to surgery and radiotherapy.

Combined Modality Therapy↗

The role of MR imaging in the selection of therapy for prostate cancer.

Combined modality staging is a methodology in which all of the pretreatment clinical factors that are found to have independent prognostic significance on multivariable analysis for predicting a given outcome (e.g., pathologic stage) are used to determine the initial management. This method of staging provides an optimized assessment of the pathologic extent of local disease prior to management, and therefore is better able to define those patients in whom local only therapy is likely to be curative. Knowing more about the pathologic extent of disease prior to therapy provides a rationale for patient selection in clinical trials that test new management strategies against the current standards. The preoperative endorectal coil MR imaging study results have been shown on multivariable analysis (which included PSA, clinical stage, and biopsy Gleason score) to provide statistically independent prognostic information about the outcomes of pathologic stage, margin status, postoperative PSA failure, and the prediction of local only failure in the positive margin patient.

Biopsy↗

Role of chemotherapy in the management of advanced thymic tumors.

Chemotherapy has an important role in the treatment of advanced thymic tumors. Early stage tumors are successfully treated with surgery. Locally advanced tumors (Masaoka stage III and IVA) are often treated with combined modality treatment including surgery, radiation, and chemotherapy. For patients with curable thymic tumors, the ability to attain a complete resection is a critical prognostic factor. Locally advanced tumors have a relatively high risk of recurrence and decreased rates of long-term survival. A multimodality approach including induction chemotherapy and postoperative radiation therapy can improve complete resection rates and long-term outcomes. Thymic tumors are chemoresponsive with optimal responses achieved with cisplatin-based combination chemotherapy. Chemotherapy with radiation can result in long-term progression-free survival for patients with locally advanced disease who remain inoperable following induction therapy. Patients with disseminated (stage IVB) thymic tumors can also have significant disease response and palliation of symptoms when treated with chemotherapy. Octreotide and corticosteroids also have shown efficacy. For best results, it is important that thoracic surgeons, radiation oncologists, and medical oncologists work together to obtain the best local control of tumor and optimal treatment of metastases.

Chemotherapy, Adjuvant↗

[Efficacy of local resection on lower rectal cancer of early stage: efficacy of report of 23 cases].

BACKGROUND & OBJECTIVE: The trans-anal local excision for lower rectal cancer of early stage may achieve the same therapeutic effect as abdominal resection. This study was to evaluate efficacy of local resection for lower rectal cancer of early stage. METHODS: Records of 23 patients with lower rectal cancer of early stage received local excision from Feb. 1989 to Apr. 1999 in our hospital were analyzed retrospectively. RESULTS: Of the 23 patients,12 were adenocarcinoma, and 11 were canceration of adenoma; 17 with tumor of stage T0, and 6 with tumor of stage T1. Three patients had local recurrence, 2 of 3 were salvaged by trans-anal local excision, and 1 of 3 was treated by abdominoperineal resection. All patients were followed-up for more than 5 years with a 5-year survival rate of 95.65%. CONCLUSION: So long as carefully considering indications of trans-anal local excision in treating patients with lower rectal cancer of early stage, good efficacy may be achieved.

Adenocarcinoma↗

Surgery of rectal tumors.

The results of surgical treatment of carcinoma of the rectum have been improved in the last decades, because of the availability of stapling device, the increasing use of adjuvant or neoadjuvant treatment and the development of endoluminal surgery. Herein we present our thirty years experience in the treatment of rectal carcinoma. It deals with 690 patients operated on, 602 with conventional surgery (87%) and 88 with local excision (13%). As regards the first subgroup, in 63 patients (10.4%) the operation was considered palliative, because there were either hepatic metastases or residual tumor; 21% of the whole number had tumor in the upper third, 40% in the middle third and 39% in the lower third. Radical resection was performed in 538 patients (89.6%); 53% of the patients underwent anterior resection and 47% underwent abdomino-perineal resection. Ninety percent of tumors located in the lower rectum were managed with abdomino-perineal resection and 97% of tumors located in the upper rectum were managed with anterior resection. Tumor of the middle rectum were treated indifferently with anterior resection or abdomino-perineal resection. Mortality was 4%; the morbidity was 33%. No statistical difference was found between anterior resection and Miles operation. Mean follow up is 6.8 years. Local recurrence was observed in 17% of patients and was more frequent after Miles operation than after anterior resection. The 5- and 10-year survival is respectively 53% and 43%; according to staging, 5-year survival is 68% for stage I, 64% for stage II, 39% for stage III and 9% for stage IV (p < 0.0001). As regard local excision, lesions usually arised from lower or middle rectum and were less than 3 cm. in the maximum diameter. Sixty per cent of patients received adjuvant or neoadjuvant treatment; we observed complete response with disappearance of the tumor in 28% of T2 patients. The toxicity was low: 3% of patients developed erithema and 21% different grades of proctitis. Mean duration of operation was 179 +/- 98 min' and hospitalization was less than 7 days in most of the patients. No mortality was recorded, while morbidity was 16% (14 patients). On pathological examination we observed 10 Tis (11%), 32 T1 (36%)28 T2 (32%) and 18 T3 (21%). Mean follow up is 3.3 years; local recurrence was related to staging and was respectively 0%, 16%, 25% and 61% (p = 0.0008). We did not observe local recurrence whenever T2 patients had neoadjuvant treatment and negative margins at i.o. pathological examination. Our findings show that anterior resection represents the most appropriate treatment for tumors of the upper and middle rectum; Miles operation should be reserved to tumors located within 5 cm. from the anal verge. Small tumors, confined to the rectal wall, can be properly treated with local excision; local treatment should be always associated to preoperative chemoradiation in tumors involving the muscular layer of the rectal wall.

Chemotherapy, Adjuvant↗

Major salivary gland tumors: treatment results and prognostic factors.

A retrospective review of 133 patients with major salivary gland carcinomas treated between 1955 and 1981 is presented. The majority of cases (104) originated in the parotid gland. The most common histological type was mucoepidermoid carcinoma (39 cases). Tumor-free interval was longest for patients with acinic cell and mucoepidermoid carcinomas. In contrast, adenoid cystic carcinoma was poorly controlled, regardless of the form of treatment. Initial control of primary major salivary gland tumors was inversely related to the presence of disease at the surgical margins. In cases with microscopic or gross disease at the surgical margins, postoperative radiation therapy controlled the tumor locally in 18 of 26 patients (69%). Postoperative radiation therapy was generally used only in cases with high-grade histologies, advanced stages, or positive surgical margins. Of the patients treated with surgery alone, 53% achieved local control, as compared to 75% of the group which received postoperative radiation therapy. Although the difference was not statistically significant, we would have expected the combined therapy group to have a lower control rate due to more advanced disease. There was a low salvage rate (22%) and a high incidence of distant metastasis (60%) in recurrent cases. The data indicates that complete surgical resection results in the best local control, with or without adjuvant radiation. When the surgical margin is inadequate and re-excision not possible, adjuvant radiation therapy appears to have a role to optimize local control and survival.

Adolescent↗

Local-regional breast cancer recurrence: prognostic groups based on patterns of failure.

The purpose of this study was to determine the outcome of breast cancer patients sustaining local-regional failure as their first site of relapse in an effort to group patients into prognostic categories. Between January 1970 and December 1992, over 4,000 patients with breast cancer were treated at our facilities with mastectomy or conservative surgery with radiation therapy (CS + RT). Two hundred thirteen patients sustained local-regional relapse without evidence of distant metastasis as their first site of failure, and they served as the population base for this study. The 213 patients with local-regional recurrence of disease were distributed as follows: 68 patients relapsed in the ipsilateral breast following CS + RT within 5 years of original diagnosis (EARLYBR). Fifty-one patients relapsed in the ipsilateral breast after 5 years from original diagnosis (LATEBR). Thirty-five patients relapsed in the chest wall within 5 years following mastectomy (EARLCW). Eighteen patients relapsed in the chest wall later than 5 years following mastectomy, and 41 patients failed in the regional lymphatics following mastectomy or CS + RT (REGREC). Patients with breast relapses were generally treated with salvage mastectomy, and patients with chest wall or regional nodal relapses were treated with radiation to the chest wall, regional nodes, or both. Systemic therapy at the time of local-regional relapse was highly individualized, ranging from observation to tamoxifen to high-dose chemotherapy with transplantation. With a median follow-up of 14 years, the overall 10-year survival for all 213 patients was 61%, and the 10-year distant metastasis-free rate was 59%. Patients with a LATEBR had a relatively favorable prognosis with a 5-year postrelapse distant metastasis rate of 80%. Patients with EARLYBR and LATECW had a similar prognosis, with a 5-year postrelapse distant metastasis rate of 61% and 65%, respectively. Patients with an EARLCW had a 5-year distant recurrence-free rate following a local relapse of 42%. Ten-year survivals from original diagnosis were 62% and 50%, respectively, and distant metastasis-free survival rates were 56% and 52%, respectively. Patients suffering REGREC following mastectomy or CS + RT carried a poor prognosis with a 10-year survival of 33% and a 10-year distant metastasis-free rate of 30%. Patients sustaining local-regional relapse as a first site of failure may be divided into prognostic groups. Patients with LATEBR have a relatively favorable prognosis. Patients with EARLYBR and CWREC have a poorer prognosis with a distant metastatic rate of approximately 50% within 5 years of local-regional relapse. Patients with REGREC have the poorest prognosis. Placing patients with breast cancer and local-regional relapse into these prognostic categories may be helpful in decision making regarding the role of systemic therapy at the time of local-regional relapse.

Adult↗

[Cryotherapy, combined drug therapy and radiotherapy in the treatment of oral cavity cancer: 3 years' experience].

The medium-term (three years) result of a multidisciplinary association treatment of carcinoma of the oral cavity has been reviewed. Treatment was Cryosurgery-polychemotherapy-ratiotherapy and the technique has been described along with the times of association in an introduction that has already been published in this review (see bibliography). Thirty patients were treated with the association because they refused or could not be submitted to surgery at the intital therapeutic action. All these patients present fairly extensive lesions and a three-year follow-up. Results were positive: 56.6% of patients showed disappearance of any objective or subjective sign of cancer and, in all cases, appreciable remission in terms of both extent and duration. The easiness of the technique is confirmed as well as the excellent conversation of the anatomical structures involved. However, a critical review of cases presenting partial failure suggest a classifications of oral carcinomatous lesions (for therapeutic purposes only) on the basis of which the condition can be treated with cryo-polychemo-radiotherapy alone or with a variation of this which provides for the addition of local exersis.

Adult↗

[Therapy of preinvasive vulvar neoplasia--standardized or individual?].

The mostly diagnosed preinvasive vulvar neoplasia is of squamous origin called "vulvar intraepithelial neoplasia" (VIN). The knowledge about the biological character of these lesions especially grade 3 is limited. Progression to invasive cancer is expected in > 40 % of untreated patients who are mostly immunocompromised or elderly. After surgical treatment of VIN the risk of invasive cancer is about 4 %. There are no significant differences in later progression and relapse rates between different surgical approaches. Risk factors for relapse are: younger age, positive margins, grade 3, multicentricity, associated intraepithelial neoplasias of the vagina and uterine cervix and immunosuppression. The aim of treatment is the removal of all lesions with negative margins. Individually adapted surgical excision is mandatory to conserve the function and figure of the vulva. Standard surgical procedures are wide local excision or laser vaporisation after safe histological characterisation.

Adult↗

Recurrent endometrial cancer after surgery alone: results of salvage radiotherapy.

PURPOSE: Postoperative irradiation of endometrial cancer patients decreases the risk of local recurrence but is associated with a number of long-term sequelae. In a proportion of patients, no immediate postoperative radiotherapy is applied and this treatment is introduced only at relapse. The aim of our study was to assess the long-term results of salvage radiotherapy in previously nonirradiated endometrial cancer patients who developed local recurrence, and to evaluate the impact of patient- and treatment-related factors on treatment efficacy. METHODS AND MATERIALS: We performed a detailed retrospective analysis of 73 endometrial cancer patients given radiotherapy for local recurrence after the initial surgery only. The mean age at diagnosis of the recurrence was 63 years (range, 39-78 years). Median time to recurrence was 11 months (range, 1-19 months). All recurrences were staged with the use of Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma. There were five (7%) Stage I patients, 43 (59%) Stage II patients, and 25 (34%) Stage III patients. Forty-four patients (60%) received both external beam irradiation (EBRT) and endovaginal brachytherapy (BRT), 17 (23%) received only BRT, and 12 (17%) received only EBRT. The mean total physical radiation dose was 75.9 Gy (range, 8-130 Gy), and the mean normalized total dose (NTD) calculated on the base of the linear-quadratic model was 86.6 Gy (range, 8.5-171.9 Gy). Median follow-up for alive patients was 8.8 years (range, 3-21 years). The impact of patient-, tumor-, and therapy-related factors on the treatment outcome was evaluated with the use of uni- and multivariate analyses. RESULTS: Three- and 5-year overall survival rates were 33% and 25%, respectively. In the univariate analysis, lower stage of recurrent disease (p < 0.0005), combined EBRT and BRT (p = 0.027), higher total radiation dose (p = 0.031), and higher NTD (p = 0.006) were significantly correlated with better survival. In the multivariate analysis, only stage of recurrent disease (p < 0.005) and high total dose (p = 0.047) were independently correlated with better survival. Lower FIGO stage of recurrence (p = 0.023) and higher total dose (p = 0.005) were also independently correlated with longer time to progression, whereas higher radiotherapy dose was the only factor correlated with better local control (p = 0.029). CONCLUSIONS: The efficacy of salvage radiotherapy in endometrial cancer patients with local failure after previous surgery is limited. Factors determining treatment outcome include advancement of the tumor at relapse and radiotherapy dose.

Adult↗

Wide excision without radiation for desmoplastic melanoma.

BACKGROUND: Adjuvant radiation has been proposed for the treatment of patients with desmoplastic melanoma, who reportedly have local recurrence rates as high as 40-60%. The authors investigated local recurrence rates at a tertiary referral center to determine the success of wide excision alone for patients with desmoplastic melanoma. METHODS: A review of a prospectively maintained melanoma clinical data base identified 65 patients between March 1997 and March 2004 with pure cutaneous desmoplastic melanoma. Complete surgical, histopathologic, and staging information was collected along with data on outcome, including local, regional, and distant recurrence and survival. RESULTS: Similar to previous reports, patients with desmoplastic melanoma had a male-to-female ratio of 2 to 1, a mean age of 65.0 years (range, 31-92 yrs), and the majority of their tumors (55%) were located on the head and neck. The mean Breslow depth at diagnosis was 4.21 mm, with 38% of tumors thicker than 4.0 mm. All patients in this series underwent wide excision without radiation therapy. Surgical margins < or = 2 cm were obtained for all trunk and extremity lesions and for 63% of head and neck lesions that measured > 1 mm in depth (63%). Margins of 1-2 cm were obtained for the remaining patients. Among 49 patients who had a minimum of 2 years of follow-up (mean, 3.7 yrs), the local recurrence rate was 4% (2 of 49 patients). Seventy-eight percent of the patients studied remained alive with no evidence of disease. CONCLUSIONS: Local recurrence rates in the current series were considerably lower than the historically reported rates. This finding suggests that, for patients with desmoplastic melanoma, wide local excision with careful attention to appropriate margins produces excellent local control rates without the need for adjuvant radiation.

Adult↗

Patterns of early treatment failure in non-metastatic nasopharyngeal carcinoma: a study based on CT scanning.

Six hundred and twenty-eight patients with non-metastatic nasopharyngeal carcinoma were staged by CT scanning and treated with radical locoregional radiotherapy. Parapharyngeal boost radiation for bulky parapharyngeal involvement, neoadjuvant chemotherapy for bulky nodal metastases, and intracavitary 192Ir treatment for local persistence of tumour after external radiotherapy were also used as appropriate. Forty-eight patients had Ho's (1978) Stage I disease (7.6%), 167 Stage II (26.6%), 312 Stage III (49.7%) and 101 Stage IV (16.1%). At 2 years after treatment, 185 patients (29.5%) had developed recurrence; 112 had distant metastases (60.5%), and 75 had local failure (40.5%). Eighty-three patients had developed distant metastases alone, 73 patients locoregional failure alone and 29 patients had both locoregional and metastatic failure. The overall 2-year actuarial distant and local failure rates were 18.4% and 12.7% respectively. Distant metastasis is the major form of treatment failure which limits early survival. Seventy-four per cent of distant metastases were not associated with locoregional recurrence and had probably arisen from pre-existing occult foci. Our data also suggest that the advent of CT scanning has improved local tumour delineation and radiotherapy planning, and hence local control.

Adolescent↗

[Study of intermittent endocrine therapy in patients presenting with biologic recurrence after radical prostatectomy or radiotherapy].

INTRODUCTION: Study of the efficacy of intermittent endocrine therapy after failure of local treatment. MATERIAL AND METHODS: 74 patients were treated for biochemical recurrence after radical prostatectomy (n = 30), radiotherapy (n = 28) or radical prostatectomy followed by radiotherapy (n = 16). Treatment (63 patients were treated by antiandrogens alone, 8 by LHRH analogue and 3 by complete androgen suppression) was continued for 6 months after obtaining undetectable PSA levels for patients after radical prostatectomy (and restarted when PSA > 4 ng/ml) or a PSA nadir < 4 ng/ml for the other patients (and restarted for PSA > 10 ng/ml). RESULTS: The duration of periods without treatment represented 50% of the total treatment cycle. With a mean follow-up of 43.8 months, the overall 5-year biochemical progression-free survival rate was 54.6%. On multivariate analysis, factors predictive of biochemical progression were age less than 70 years (p = 0.05), Gleason score greater than or equal to 8 (p = 0.038) and the presence of lymph node metastases (p = 0.05). CONCLUSION: Intermittent endocrine therapy is a treatment option for patients with recurrence after local treatment. Candidates for intermittent endocrine therapy must be over the age of 70, with localized adenocarcinoma and a Gleason score less than or equal to 7.

Age Factors↗

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

BACKGROUND: Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18F-deoxyglucose (FDG)-avid tumors. METHODS: Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. RESULTS: Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. CONCLUSIONS: The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

Adolescent↗