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[Clinical characteristics and multivariate analysis of prognostic factors in recurrent laryngeal carcinoma].

BACKGROUND & OBJECTIVE: The recurrence is an important factor affecting the prognosis of laryngeal carcinoma. There are few reports on the clinical characteristics and the prognostic factors of recurrent laryngeal carcinoma. The purpose of this study was to analyze the clinical features and prognostic factors of recurrent laryngeal carcinoma. METHODS: The data of 80 patients with recurrent laryngeal carcinoma between 1990 and 1997 were retrospectively investigated. Survival analysis was performed by Kaplan-Meier method; comparison among/between groups was performed using log-rank test; multivariate analysis was carried out using Cox proportional hazard model. RESULTS: The recurrence sites included locoregional recurrence, neck lymph node and distant metastases. The 3-year and 5-year overall survival rates for patients with recurrent laryngeal carcinoma were 50.6% and 34.6%, respectively. The 5-year disease-specific survival rates for the patients treated with surgery, surgery + radiotherapy, and surgery +chemotherapy (30 cases) was 73%. The recurrence of laryngeal carcinoma were developed within 1-156 months, the median time of recurrence was 11 months; there were 36 locoregional recurrence, 36 neck lymph node recurrence, 4 locoregional recurrence associated with neck lymph node recurrence, 1 locoregional recurrence associated with distant metastases, 3 neck lymph node recurrence associated with distant metastases. Univariate analysis revealed that the factors impacting the prognosis were recurrent site, duration of recurrence gaps, treatment modality of recurrence, and age (P< 0.05). The neck lymph node recurrence group, peristomal recurrence group, distant metastases group, radiotherapy and chemotherapy after recurrence group had a poorer prognosis than locoregional recurrence group, larynx recurrence group, without distant metastases group, and surgery group (P< 0.05). Multivariate analysis showed that age > or =60 years old, duration of recurrence gap < 12 months, distant metastases and radiotherapy or chemotherapy modality after recurrence were independently associated with decreased survival rates (P< 0.05). CONCLUSION: Surgery or surgery dominated multi-modality therapy was the principal treatment modality for recurrence laryngeal carcinoma. Age > or =60 years old, duration of recurrence gap < 12 months, distant metastases and salvage therapy by radiotherapy and chemotherapy but not surgery were independent factors affecting the prognosis.

Adult↗

Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis.

PURPOSE: The outcome of patients with local-regional breast cancer recurrence after mastectomy often is described as fatal. However, certain subgroups with favorable prognoses are thought to exist. To determine these favorable subgroups, we analyzed prognostic factors for their influence on postrecurrence survival by univariate and multivariate analysis. METHODS AND MATERIALS: Between 1979 and 1992, 145 patients with their first isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases were treated at the Department of Radiation Oncology of the University of Wurzburg. Thirty-nine percent of patients (n = 67) had had postmastectomy radiotherapy, representing 7% of patients who had received routine postmastectomy irradiation at our institution. Systemic adjuvant hormonal therapy had been applied in 24% and systemic chemotherapy in 19% of patients. Several combinations were used. Treatment of recurrences consisted of surgical tumor excision in 74%, megavoltage irradiation in 83%, additional hormonal therapy in 41%, and chemotherapy in 12% of patients, employing different combinations. Local control in the recurrent site was achieved in 86%. Median follow-up for patients alive at the time of analysis was 8.9 years after recurrence. We tested different prognostic factors, including prior treatment and treatment of recurrence, for their influence on postrecurrence survival, using univariate and multivariate analysis. RESULTS: Eighty-two of the 145 patients (57%) developed distant metastases within the follow-up period. Metastases-free rate was 42% at 2 years and 36% at 10 years following recurrence. With development of distant metastases, the survival rate deteriorated. Recurrences appeared within the first 2 years from primary surgery in 56% of patients, and in 89% within 5 years. Overall, 2-year and 5-year survival rates following local-regional recurrence were 67% and 42%, respectively. Univariate analysis revealed statistically significant worsening of survival rates for pT3 + 4 primary tumors, primary axillary lymph node involvement, tumor grading 3 + 4, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, negative estrogen (ER) and progesterone (PR) hormonal receptor status, postmastectomy chemotherapy and hormonal therapy, short time to recurrence (< 1 year), combined recurrences and supraclavicular site of recurrence, non-scar recurrence, size of the largest recurrent nodule > 5 cm, multiple recurrent nodules, no surgical excision of recurrence, small target volume of irradiation, chemotherapy for recurrence, and no local control within the recurrence site. The 2-year and 5-year survival rates ranged from 68% to 94%, and from 33% to 65%, respectively, in the favorable subgroups compared to 2-year and 5-year survival rates ranging from 20% to 59% and 0% to 35%, respectively, in the unfavorable subgroups. Multivariate analysis showed that site of recurrence and number of recurrent nodules have the strongest influence on postrecurrence survival, but time to recurrence, age at time of recurrence, local control in recurrent site as well as primary pT and axillary status, and the presence of tumor necrosis in the primary tumor specimen showed additional independent influences on survival. Thus, we identified a highly favorable subgroup of patients with a single chest wall or axillary recurrent nodule (in a patient aged > 50 years), a disease-free interval of > or = 1 year, pT1-2N0 primary tumor, and without tumor necrosis, and whose recurrence is locally controlled. This group (12 patients) had 5- and 10-year survival rates of 100% and 69%, respectively. CONCLUSION: We conclude that locoregional recurrence of breast cancer following mastectomy is not always a sign of systemic disease. Our data support previous findings, that subgroups with favorable prognosis exist and they still have a chance for cure, demanding comprehensive local treatment. (ABSTR

Analysis of Variance↗

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer.

PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.

Adult↗

Patterns of recurrence of intussusception in children: a 17-year review.

PURPOSE: Patterns of recurrence of intussusception (INT) were reviewed to determine whether changes in management have affected the rate and patterns of recurrence as well as long-term outcome in children with multiple (i. e., 2 or more) recurrences. MATERIALS AND METHODS: Review was done of 763 children with 876 intussusceptions, including (1) recurrence rate, (2) patterns of recurrence (number of and interval between recurrences), (3) reducibility, (4) pathologic lead points (PLP), (5) operative findings and (6) long-term follow-up in those with multiple recurrences. RESULTS: Above features (1)-(6) were the same in those managed with barium enema (1979-1985) and those managed with air enema (1985-1996). Overall recurrence rate was 9 %; 11 % with barium enema and 8 % with air enema. Sixty-nine patients had 113 recurrences: 47/69 (68 %) and 1 recurrence and 22/69 (32 %) had multiple recurrences. Multiple recurrences presented as isolated episodes or in clusters up to 8 years. Reducibility was 100 % for initial INT and 95 % for recurrent episodes; there were no perforations. Surgery, in 4 with irreducible recurrence, revealed no PLP. PLP were present in 5 (8 %): 2 (4 %) with 1 recurrence and 3 (14 %) with multiple recurrences. No pattern of recurrence was predictive for PLP. Long-term follow-up (up to 15 years) available in 11 with multiple recurrences revealed a favourable outcome. CONCLUSIONS: Rates and patterns of recurrence did not change with altered management. Because of the high reduction rate of recurrences, lack of perforation and favourable long-term follow-up, we recommend radiological reduction for recurrent INT. Multiple recurrences are not a contraindication. A careful search for PLP is mandatory. Surgery should be reserved for irreducible recurrences or for demonstrated PLP.

Adolescent↗

Breast cancer recurrence after immediate reconstruction: patterns and significance.

Local recurrence of cancer after mastectomy and immediate breast reconstruction is generally regarded as a poor prognostic indicator. This study was conducted to identify specific patterns of local recurrence following reconstruction and to determine their biological significance. The records of all patients who had undergone immediate breast reconstruction at The University of Texas M. D. Anderson Cancer Center between June 1, 1988, and December 31, 1998, were reviewed. The records of patients who had local tumor recurrence were then carefully analyzed. During this 10-year period, a local recurrence of cancer was found to have developed in 39 of 1694 patients (2.3 percent). Most recurrences were in the skin or subcutaneous tissue (n = 28; 72 percent), and the remainder were in the "chest wall" (n = 11; 28 percent), as defined by skeletal or muscular involvement. Transverse rectus abdominis myocutaneous flaps were used most often in both groups, but latissimus dorsi myocutaneous flaps and implant techniques were also used in some patients. Patients with subcutaneous tissue recurrence had an overall survival rate of 61 percent at follow-up of 80.8 months, compared with patients with chest wall recurrence, whose survival rate was 45 percent at similar follow-up. Metastases were less likely to develop in patients with subcutaneous tissue recurrence than in those with chest wall recurrence (57 percent versus 91 percent; p = 0.044); the former group also had a greater chance of remaining disease-free after treatment of the recurrence (39 percent versus 9 percent), respectively. Metastasis-free survival was higher in patients with subcutaneous tissue recurrence than with chest wall recurrence (2-year and 5-year survival: 52 and 42 percent versus 24 and 24 percent; p = 0.04). In both groups, the time to detection of the recurrence was similar (subcutaneous tissue recurrence, 27.1 months, versus chest wall recurrence, 29.5 months). Distant disease did not develop in one patient only in the chest wall recurrence group; this patient remained disease-free at 70 months. From these results, it was concluded that (1) not all local recurrences are the same: patients with subcutaneous tissue recurrence have better survival rates, a decreased incidence of metastases, and a greater chance of remaining disease-free than do those with chest wall recurrence; (2) immediate breast reconstruction (although potentially, it can conceal chest wall recurrence) does not seem to delay the detection of chest wall recurrence; and (3) even if a chest wall recurrence develops, it is highly associated with metastatic disease, and the survival rate is not likely to have been influenced by earlier detection. These data support the continued use of immediate breast reconstruction without fear of concealing a recurrence or influencing the oncologic outcome.

Adult↗

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.

BACKGROUND: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS: After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS: Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.

Adult↗

Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131)

OBJECTIVE: This retrospective study compared treatment and survival of patients with recurrent well-differentiated thyroid cancer that was diagnosed exclusively by I131 scanning, or by clinical examination. SUMMARY BACKGROUND DATA: Despite the usual excellent prognosis of differentiated thyroid cancer, approximately half of patients who developed a recurrence eventually succumb to the disease. It has been speculated, but not proven, that recurrent disease detected solely by I131 scanning may offer a better prognosis than recurrences detected clinically and be amendable to I131 ablative therapy without the addition of surgical resection. METHODS: Seventy-four cases of recurrent differentiated thyroid cancer were identified retrospectively and examined regarding the location of recurrence, mode of detection of recurrent disease, treatment of recurrence, and outcome of patients. Using Fischer exact testing, outcome results for recurrences detected exclusively by I131 scan was compared to that of clinically diagnosed recurrences; among clinically detected recurrent cases, treatment with surgery only was compared to surgery/I131 ablation. Kaplan-Meier actuarial survival curves were generated for clinically detected recurrent cancer treated by surgery only and compared to those treated by surgery and I131 ablation using Gehan-Wilcoxon and log-rank analysis. RESULTS: Recurrences located most commonly were regional (53%), followed by local (28%), distant metastasis (13%), and combined locoregional (6%). Among patients whose recurrence was detected scintigraphically, only 9.5% had persistence of disease or were dead of disease compared to 54.0% of patients with clinically detected recurrences. Radioactive iodine ablation in scintigraphically detected recurrences salvaged 18 of 20 patients (90%). Among clinically detected recurrences, surgery alone salvaged 12 of 21 patients (57%), whereas the addition of I131 ablation to surgery salvaged only 3 of 15 patients (20% p = 0.05). CONCLUSION: The probability of dying or living with persistent disease after treatment of recurrent thyroid cancer is less for I131 detected recurrences compared to clinically diagnosed recurrences; I131 ablation without surgery constitutes adequate therapy for scintigraphically detected recurrences. In clinically recurrent disease, the addition of I131 ablation to curative resection does not appear to improve survival.

Actuarial Analysis↗

Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means?

OBJECTIVES/HYPOTHESES: Salvage surgery is widely viewed as a "double-edged sword." It is the best option for many patients with recurrent cancer of the upper aerodigestive tract, especially when original therapy included irradiation, yet it may provide only modest benefit at high personal cost to the patient. The stakes are high because alternatives are of limited value. The primary objective of this study was to fully assess the value of salvage surgical procedures in the treatment of local and regional recurrence. The following hypotheses were developed to focus the study design and data analysis. 1) The efficacy of salvage surgery correlates recurrent stage, recurrent site, and time to presalvage recurrence. 2) The economic and noneconomic costs of salvage surgery increase with higher recurrent stage. 3) Information relating the value of salvage surgery to recurrent stage and recurrent site will be useful to these patients and the physicians who treat them. STUDY DESIGN: Two complimentary methods of investigation were used: a meta-analysis of the published literature and a prospective observational study of patients undergoing salvage surgery for recurrent cancer of the upper aerodigestive tract. METHODS: The meta-analysis combined 32 published reports to obtain an estimate of average treatment effect for salvage surgery with regard to survival, disease-free survival, surgical complications, and operative mortality. The prospective observational study included detailed data in 109 patients who underwent salvage surgery. In addition to parameters studied in the meta-analysis, we obtained baseline and interval quality of life data (Functional Living Index for Cancer [FLIC] scores), baseline and interval performance status evaluations (Performance Status Scale for Head and Neck Cancer Patients [PSS head and neck scores]), length of hospital stay, and hospital and physician charges, and related this data primarily to recurrent stage, recurrent site, and time to presalvage recurrence. RESULTS: The weighted average of 5-year survival in the meta-analysis was 39% in 1,080 patients from 28 different institutions. In the prospective study, median disease-free survival was 17.9 months in 109 patients, and this correlated strongly with recurrent stage, weakly with recurrent site, and not at all with time to presalvage recurrence. Noneconomic costs for patients and economic costs correlated with recurrent stage, but not with site. Baseline FLIC and PSS head and neck scores correlated with recurrent stage, but not with site. After salvage surgery the percentage of patients reaching or exceeding baseline was 51% for FLIC scores, and this differed significantly with recurrent stage. Postoperative interval "success" in PSS head and neck subscale scores for diet and eating in public also correlated with recurrent stage. CONCLUSIONS: Overall, the expected efficacy for salvage surgery in patients with recurrent head and neck cancer was surprisingly good, but success was limited and costs were great in stage III and, especially, in stage IV recurrences. A strong correlation of efficacy and noneconomic costs with recurrent stage allowed the creation of expectation profiles that may be useful to patients. Additional systematic clinical research is needed to improve results. In the end, the decision to undergo salvage surgery should be a personal choice made by the patient after honest and compassionate discussion with his or her surgeon.

Carcinoma, Squamous Cell↗

Morphogenesis and clinicopathologic characteristics of recurrent carotid disease.

The histopathologic characteristics of primary plaques and recurrent carotid disease were studied in 32 patients. These data were related to symptoms, recurrence interval (6 to 176 months), arteriographic anatomy, and in situ operative findings. A striking predilection was noted for recurrent lesions to be located in the internal carotid artery near the origin, but still within the confines, of the original endarterectomy site and suture line. Although recurrence was frequently associated with a long primary arteriotomy, evidence of technical faults or periarterial fibrosis was rare. Early recurrent lesions (recurrence interval less than 36 months, n = 13) had significantly more smooth muscle cells and proteoglycans (p less than 0.001) than late recurrent lesions (recurrence interval greater than 36 months, n = 19). As previously reported, features of atherosclerosis (abundant collagen, calcium deposits, and foam cells) were more pronounced in late recurrences (p less than 0.001). However, the histopathologic differentiation between early and late recurrent carotid disease was indistinct. A continuum was noted whereby characteristics of late recurrent lesions increased in proportion to recurrence interval. All recurrent lesions were easily distinguished from primary plaques in that recurrences had a less orderly arrangement of all elements and lacked the classic topographic features of advanced atherosclerosis. An important feature that differentiated primary and recurrent lesions was the presence of surface and intraplaque thrombus in 90% of recurrent lesions (p less than 0.001). In early recurrent disease, luminal surface thrombus was striking; this was frequently platelet-rich and showed organization devoid of neovascularity. Intraplaque thrombus was more common in late recurrent disease, consisted almost entirely of fibrin, and was often contiguous with luminal surface thrombus. No discernible relationships were noted between thrombus associated with recurrent lesions and the presence or absence of symptoms, treatment with antiplatelet agents, and hypertension. This finding suggests that thrombus was a continuous and intrinsic component of recurrent disease rather than a secondary, complicating feature. Recurrent carotid disease is a progressive lesion that stems from ongoing thrombogenesis occurring at the endarterectomy site. Organized thrombus and smooth muscle cell proliferation comprise the bulk of the lesion, which undergoes atherosclerotic change with time.

Aged↗

Stomal recurrence in patients with T1 glottic cancer after salvage laryngectomy for radiotherapy failures: role of p53 overexpression and subglottic extension.

The role of p53 overexpression in the development of stomal recurrence was studied in patients with T1 glottic cancer who had undergone salvage laryngectomy after primary radiotherapy failure (first recurrence). The role of subglottic extension of the recurrent tumor in the development of stomal recurrence was also studied. One hundred fourteen patients with T1 squamous cell carcinoma of the glottic larynx were irradiated with curative intent. A local recurrence (first recurrence) developed in 23 patients (20%), and salvage laryngectomy was performed for 20 of these patients. No postlaryngectomy radiation therapy was included in the treatment of recurrences. Several risk factors thought to be significant in the development of stomal recurrence were analyzed in these 20 patients. Prognostic factors analyzed include: p53 overexpression in the preradiation biopsy specimen, subglottic extension of the first recurrence, thyroid cartilage and lymph node involvement at the time of first recurrence, emergency tracheostomy performed before salvage laryngectomy, and the laryngectomy procedure performed for first recurrence. Presence of p53 protein in the preradiation biopsy specimen of laryngeal cancer did not show any adverse effect on the development of stomal recurrence. Stomal recurrence developed in 27% of patients with positive biopsies and in 20% of patients with negative biopsies (p = 1.00). Subglottic extension of the first recurrence was associated with an increased incidence of stomal recurrence. Rates of stomal recurrence were 6% in patients without subglottic extension and 100% in patients with subglottic extension (p = 0.001). All other risk factors studied showed no effect on stomal recurrence. In this study, p53 overexpression showed no effect on the development of stomal recurrence after salvage laryngectomy in patients with T1 glottic cancer. Conversely, subglottic extension of the recurrence was found to be strongly associated with stomal recurrence. All other factors analyzed showed no effect on stomal recurrence.

Carcinoma, Squamous Cell↗

Recurrence pattern for superficial bladder cancer.

AIM: Patients with superficial bladder tumors sometimes have long recurrence-free intervals. We evaluated whether patients with long recurrence-free periods had subsequent recurrences. We also clarified how these patients should be followed. MATERIALS AND METHODS: We enrolled 244 patients with superficial bladder cancer (62 pTa and 182 pT1) treated by transurethral resection of bladder tumor (TURBT) and adjuvant chemotherapy with pirarubicin. Median follow up was 75.5 months. Patients were stratified by the length of their recurrence-free interval. RESULTS: Recurrences occurred in 124 patients (50.8%). Of 185 patients who did not have a recurrence for the first 3 years, subsequent recurrences occurred in 65 patients; in more than half the first recurrence developed after 5 years or more. Ta tumors had a low recurrence rate (14.5%) with the first recurrence often developing after a long recurrence-free period. Of 40 patients who remained recurrence-free for 3 years or more after at least one recurrence occurred, 16 patients (40%) had subsequent recurrences. Furthermore, most of these patients who remained free of recurrence for more than 5 years eventually had a recurrence. The overall progression rate was 15.6%, and this did not relate to the length of the recurrence-free interval. CONCLUSION: When patients did not have a recurrence for the first 3 years, tumors subsequently often recurred, even in pTa tumors. In patients with at least once recurrence, subsequent recurrences appear to occur irrespective of the length of the recurrence-free period. Thus, we recommend that all patients with superficial bladder tumors be followed for as long as possible.

Adult↗

Patterns of recurrence in patients with high-grade soft-tissue sarcomas.

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years' minimum follow-up.

PURPOSE: In this pilot study of high-dose-rate brachytherapy to the lumpectomy site as the sole radiation, ipsilateral and contralateral breast recurrences are documented with specific attention to the location of recurrence relative to the lumpectomy site. METHODS: Between March 1992 and January 1996, 39 patients with T1 (32 patients) and T2 breast cancers received 37.2 Gy in 10 fractions (b.i.d.) over 1 week prescribed to a volume encompassing the surgical clips. Thirteen received adjuvant tamoxifen, and 4 received chemotherapy. Follow-up included annual bilateral mammograms and clinical breast examination every 3 to 6 months. Whereas 13 patients had intraoperative implantation of the lumpectomy site, 26 had postoperative implantation. The latter group and 7 of the former group had surgical clips marking the lumpectomy site, which allowed estimates of the distance of any ipsilateral breast recurrence from the lumpectomy site, using the mediolateral and cranio-caudad mammographic views. RESULTS: At a median follow-up of 91 months, 33 women are alive, 4 have died of disease, and 2 have died of other causes. The 5-year actuarial rate of ipsilateral breast recurrence was 16.2%. Of 6 ipsilateral recurrences, 2 occurred within the lumpectomy site (in-field recurrences). One of the 2 patients had a 1-mm microscopic margin at initial diagnosis; the recurrence was a 3.5-mm microscopic focus of duct carcinoma in situ. The other patient had a 1.5-cm, high-grade infiltrating mammary carcinoma with no residual at wider resection at first diagnosis; the 5-mm invasive recurrence was also of high grade. Four women developed invasive recurrences at least 1.6 cm or more from the lumpectomy site (out-of-field recurrences). Two of these women had gross multifocal recurrences with two cancers in each patient; 1 of the 2 patients had an extensive intraductal component at initial diagnosis. The estimated nearest distances between the out-of-field recurrences and the surgical clips were 1.6, 5.5, 7.7, and 12.0 cm. All ipsilateral breast recurrences were salvaged by mastectomy (4 patients) or by repeat lumpectomy (2 patients) and whole-breast radiation. The interval postdiagnosis to ipsilateral recurrence ranged from 20 months to 58 months. There were two contralateral breast recurrences at intervals of 34 and 36 months; 1 of these patients also had a multifocal, ipsilateral recurrence at 58 months, as previously described. Among patients with any breast recurrence, 1 patient had a family history of prostate cancer; there was no family history of breast or ovarian cancer. Of 17 patients who received adjuvant systemic therapy, only 1 had a breast recurrence. CONCLUSIONS: In this pilot study, breast recurrences outside of the lumpectomy site were the predominant pattern of recurrence.

Adult↗

[Locoregional recurrences after conservative treatment of breast cancer stage I-II].

BACKGROUND: Since 1992 conservative treatment of breast cancer (stage I and II: clinical TNM) has been established as an alternative to mastectomy in our hospital. The aim of this retrospective study was to analyse locoregional recurrence features and to compare prognosis with regard to to site of recurrence. METHOD: Between 1987 and 1993, 489 patients with breast cancer (stages I and II) were treated with conservative surgery and radiation therapy at the Hospital Sant Pau of Barcelona. Mean follow-up was 58.8 months [between 12-144]. 35 patients developed locoregional recurrence. We considered two groups: local recurrence in breast only; and locoregional recurrence such as nodal recurrence with or without simultaneous breast recurrence. Diagnosis was confirmed by histopathologic analysis. An extensive study was performed in all patients to rule out distant metastasis. Last follow-up was December 1999. RESULTS: The locoregional recurrence rate after conservative treatment was 7.5% and that of local recurrence was 3.06%. Recurrences were diagnosed in 80% of patients by physical examination, while 20% of patients had noticed the tumor recurrence themselves. Histologic grade III tumors had a higher number of locoregional recurrences than local recurrences (p = 0.030). Locoregional recurrences had lower overall survival rate (p = 0.0005), lower disease-free survival rate (p = 0.0012) and shorter time period without distant metastasis (p < 0.0005) than local recurrences. CONCLUSIONS: Most recurrences were diagnosed by clinical examination during follow up. Histologic grade III was related to locoregional recurrences. Local recurrences had a better prognosis than locoregional recurrences.

Adult↗

Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.

BACKGROUND: Current approaches to adjuvant treatment after resection of gallbladder carcinoma (GBCA) and hilar cholangiocarcinoma (HCCA) are based on an incomplete understanding of the recurrence patterns of these diseases. Through an in-depth analysis of the sites of initial recurrence after resection of GBCA and HCCA, the current study aimed to highlight differences in the biology of these tumors and to provide further insight for adjuvant therapeutic strategies. METHODS: Patients with either GBCA or HCCA who underwent a potentially curative resection were identified prospectively from a maintained database. Specific sites of initial disease recurrence were identified retrospectively and categorized as locoregional (resection margin, porta hepatis, or retroperitoneal lymph nodes) or distant (peritoneal, extraabdominal, or discontiguous liver metastases). Differences in disease recurrence patterns, time to disease recurrence, and overall and site-specific survival were analyzed. RESULTS: Between May 1990 and August 2001, 177 patients underwent potentially curative resection, 97 for GBCA and 80 for HCCA. Disease recurrence and follow-up data were available for 156 patients (80 with GBCA and 76 with HCCA). The median time to disease recurrence was shorter for patients with GBCA compared with patients with HCCA (11.5 vs. 20.3 months; P = 0.007). Overall, 52 (68%) patients with HCCA and 53 (66%) patients with GBCA had disease recurrene at a median follow-up of 24 months. Of those who developed disease recurrence, isolated locoregional disease as the first site of failure occurred in 15% of patients with GBCA compared with 59% of patients with HCCA (P < 0.001). By contrast, an initial GBCA recurrence involving a distant site, with or without concomitant locoregional recurrence, occurred in 85% of patients compared with 41% of patients with HCCA (P < 0.001). This pattern of disease recurrence was diagnosis specific and did not change significantly when patients were stratified by several clinicopathologic factors, including disease stage and its component variables. Using multivariate analysis, diagnosis was an independent predictor of the site of disease recurrence. Among patients who experienced disease recurrence, survival was greater among the patients with HCCA compared with patients with GBCA (29 months vs. 20.6 months, respectively; P = 0.037). For both tumors, the site of initial disease recurrence had no apparent impact on survival time. CONCLUSIONS: After resection, recurrent GBCA is much more likely than recurrent HCCA to involve a distant site. GBCA is also associated with a much shorter time to recurrence and a shorter survival period after recurrence. The results demonstrated significant differences in the clinical behavior of these tumors and suggested that an adjuvant therapeutic strategy targeting locoregional disease, such as radiotherapy, is unlikely to have a significant impact in the overall management of GBCA. Conversely, there is at least some rationale for such an approach in patients with HCCA based on the pattern of initial recurrence.

Adult↗

Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome.

OBJECTIVE AND METHODS: This study reports clinicopathologic features, treatment, and outcome of 30 recurrent thymomas out of 266 totally resected thymomas. RESULTS: The mean disease-free interval to recurrence was 86 months. Recurrence occurred less frequently and after a longer disease-free interval after resection of encapsulated versus invasive thymomas. The presence of associated myasthenia gravis did not affect recurrence proportion, disease-free interval, or survival after recurrence. A local recurrence occurred in 11 patients, 17 patients had a distant recurrence, and the extent of the recurrence could not be determined in 2 cases. Surgical treatment of the recurrent tumor was attempted in 16 cases, and a total resection was possible in 10 cases; exclusive radiotherapy was done in 11 cases. Overall 5- and 10-year survivals were 48% and 24%, respectively. In a univariate analysis, survival was significantly better in the presence of a local recurrence and in case of a total resection of the recurrent tumor. The use of adjuvant therapy after the resection of the initial thymoma had no effect on reducing the incidence of recurrence, in prolonging the disease-free interval, or in improving survival after the development of the recurrence. In a multivariate survival analysis, significant prognostic factors were the presence of a local recurrence and total resection of the recurrent tumor. CONCLUSIONS: Surgical resection is recommended in patients with recurrent thymoma. Local recurrence and total resection of the recurrent tumor are associated with excellent prognosis. A poor prognosis may be anticipated in the presence of distant recurrence and when radical surgical treatment is not done.

Adult↗

Factors affecting recurrence after surgery for Crohn's disease.

Although in Crohn's disease post-operative recurrence is common, the determinants of disease recurrence remain speculative. The aim of this study was to examine factors affecting post-operative recurrence of Crohn's disease. A Medline-based literature review was carried out. The following factors were investigated: age at onset of disease, sex, family history of Crohn's disease, smoking, duration of Crohn's disease before surgery, prophylactic medical treatment (corticosteroids, 5-amino salicylic acid (5-ASA) and immunosuppressants), anatomical site of involvement, indication for surgery (perforating or non-perforating disease), length of resected bowel, anastomotic technique, presence of granuloma in the specimen, involvement of disease at the resection margin, blood transfusions and post-operative complications. Smoking significantly increases the risk of recurrence (risk is approximately twice as high), especially in women and heavy smokers. Quitting smoking reduces the post-operative recurrence rate. A number of studies have shown a higher risk when the duration of the disease before surgery was short. There were, however, different definitions of 'short' among the studies. Prophylactic corticosteroids therapy is not effective in reducing the post-operative recurrence. A number of randomized controlled trials offered evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative recurrence. Recently, the therapeutic efficacy of immunosuppressive drugs (azathioprine and 6-mercaptopurine) in the prevention of post-operative recurrence has been investigated and several studies have reported that these drugs might help prevent the recurrence. Further clinical trials would be necessary to evaluate the prophylactic efficacy of immunosuppressants. Several studies showed a higher recurrence rate in patients with perforating disease than in those with non-perforating disease. However, evidence for differing recurrence rates in perforating and non-perforating diseases is inconclusive. A number of retrospective studies reported that a stapled functional end-to-end anastomosis was associated with a lower recurrence rate compared with other types of anastomosis. However, prospective randomized studies would be necessary to draw a definite conclusion. Many studies found no difference in the recurrence rates between patients with radical resection and non-radical resection. Therefore, minimal surgery including strictureplasty has been justified in the management of Crohn's disease. In this review, the following factors do not seem to be predictive of post-operative recurrence: age at onset of disease, sex, family history of Crohn's disease, anatomical site of disease, length of resected bowel, presence of granuloma in the specimen, blood transfusions and post-operative complications. The most significant factor affecting post-operative recurrence of Crohn's disease is smoking. Smoking significantly increases the risk of recurrence. A short disease duration before surgery seems, albeit to a very minor degree, to be associated with a higher recurrence rate. 5-ASA has been shown with some degree of confidence to lead to a lower recurrence rate. The prophylactic efficacy of immunosuppressive drugs should be assessed in future. A wider anastomotic technique after resection may reduce the post-operative recurrence rate, though this should be investigated with prospective randomized controlled trials.

Age of Onset↗

Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma.

INTRODUCTION: In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing. METHODS: Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with &#x2265; 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index. RESULTS: Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson-Steiner grading and greater retention of CTNNB1, TP53, ARID1A, and KEAP1 mutations. The number of shared variants (median: 115 vs. 0, and p&#xa0;<&#xa0;0.001) and the Jaccard index (median: 0.44 vs. 0.00 and p&#xa0;<&#xa0;0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation. CONCLUSION: Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.

clonal relapse↗