A Reasonable Definition of Oligo-Recurrence in Non–Small-Cell Lung Cancer

BackgroundThe concept of oligo-recurrence in non–small-cell lung cancer (NSCLC) has been suggested to describe the possibility of achieving long-term survival or even cure with local therapy for recurrence despite having recurrent disease. Oligo-recurrence involves a limited number of metachronous recurrences that can be treated with local therapy. However, the number of recurrences that constitutes an oligo-recurrence has varied among studies and remains to be defined. The aim of this study was to elucidate the number of recurrences that constitutes an oligo-recurrence in NSCLC.Patients and MethodsWe retrospectively reviewed 577 patients with NSCLC who had underwent complete resection and developed recurrence between 1990 and 2009, and these patients were evaluated.Patients were categorized according to the number of recurrences, and postrecurrence survival (PRS) was compared between groups.ResultsAltogether, 270 patients underwent local therapy for all recurrent lesions. In these patients, sex (female), histological type (adenocarcinoma), gene mutation status, recurrence-free interval <1 year, and presence of 1 or 2 recurrences were factors associated with prolonged PRS. Additionally, all patients who maintained a cancer-free status for at least 5 years after treatment for recurrence and were considered possibly cured, had 1 or 2 recurrences.ConclusionAmong patients receiving radical local therapy, the PRS was particularly longer among those with 1 or 2 recurrences, and these patients were able to aim for postrecurrence cure. Thus, a reasonable threshold to define oligo-recurrence in NSCLC is 1 or 2 recurrences that can be treated with local therapy.     

Metastatic potential of dermatofibrosarcoma protuberans with fibrosarcomatous change

Dermatofibrosarcoma protuberans (DFSP) is a relatively uncommon fibrohistiocytic tumor that is locally aggressive. DFSP is associated with frequent local recurrences but rarely metastasizes. It has been suggested that fibrosarcomatous change within a dermatofibrosarcoma protuberans (DFSP-FS) is associated with increased risk of local recurrence and distant metastases. Metastases remain rare, however, and are typically preceded by multiple local recurrences. We report a rare case of a DFSP-FS metastasis to the head of the pancreas without any preceding local recurrence.     

影响乳腺癌术后局部复发因素的分析

选择主要临床与组织病理学因素和治疗因素，观察对乳腺癌术后局部复发的影响，２４２２例女性浸润性乳腺癌病人中，３年内局部复发１８２例，复发率７．５％，经过Ｌｏｇｉｓｔｉｃ回归的方法统计，年龄，绝经状态和病理类型不是影响乳腺癌术后局部复发的主要因素，而原发肿块情况，腋下淋巴结转移与否和雌激素受体状态对乳腺癌术后的局部复发的影响有意义，尤以肿块侵犯皮肤或胸壁，腋下淋巴结转移融合，雌激素受体阴性者术后复发的     

Local recurrence of stage 1 and 2 breast cancer after skin-sparing mastectomy and immediate breast reconstruction in a 15-year series

Aims

Since the introduction of skin-sparing mastectomy (SSM) in 1991 concerns on local control and recurrence rates have been discussed in the literature. The aim of this study is to examine in particular incidence of local recurrence in a 15-year consecutive series of breast cancer patients having undergone SSM and immediate breast reconstruction (IBR) at a single population-based institution.

Methods

One hundred and forty-six consecutive patients with either stage 1 or 2 breast cancer who underwent SSM followed by IBR from 1992 to 2006 were included in this study. A retrospective review of patient records was conducted.

Results

During a mean follow-up time of 51 months, four local recurrences of the native breast skin were accounted for. In addition, three regional lymph node recurrences and four systemic recurrences took place. All of the local and regional recurrences were handled by salvage surgery followed by adjuvant oncological therapies. During a mean follow-up of 35 months after the detection and treatment of the locoregional recurrences none of the patients developed new recurrences.

Conclusions

Our present study concludes that SSM followed by IBR seems oncologically sound procedure for stage 1 and 2 breast cancer patients. In addition, local recurrences and regional lymph node recurrences are not always associated with systemic relapse.     

Local and distant failures after limited surgery with positive margins and radiotherapy for node-negative breast cancer

PURPOSE: To determine the outcome of patients with positive margins after lumpectomy for breast cancer and to address the issue of the relationship between local recurrences and distant metastasis in the absence of chemotherapy. METHODS AND MATERIALS: Among 3697 patients with primary breast cancer, we retrospectively analyzed 152 patients who had undergone conservative surgery with axillary dissection, had infiltrating carcinomas with positive margins, were node-negative, and received radiotherapy without chemotherapy. One-third received hormonal therapy. Endpoints were local failure and distant metastasis. Median follow-up was 72 months. RESULTS: Five- and 10-year recurrence-free survival were 0.80 and 0.71 respectively for local recurrences, and 0.85 and 0.73 respectively for metastasis. Infiltrating carcinoma on the margins was associated with early local relapse as opposed to intraductal carcinoma. Local and distant recurrences had similar patterns of yearly-event probabilities. Hazard of relapsing from metastasis was 2.5 times higher after a local recurrence. In the multivariate analysis, negative estrogen receptors (ER-)(p = 0.0012), histologic multifocality (p = 0.0028), and no hormonal therapy (p = 0.017) predicted local relapses, while ER- (p = 0.004) and pathologic grade (p = 0.009) predicted metastasis. Hormonal therapy did not prevent early local recurrences. CONCLUSION: In this population, reexcision is advisable for local purposes and because the data support the hypothesis that local and distant recurrences are tightly connected.     

DNA ploidy of primary breast cancer and local recurrence after breast-conserving therapy.

The value of DNA-flow cytometry and clinico-pathological prognostic factors for the prediction of local recurrences after breast-conserving therapy (BCT) were evaluated in a retrospective study. Thirty-one patients with a local recurrence were compared with 31 matched patients without a local recurrence. Morphology and DNA-indices of the local recurrences and their corresponding primary tumours were compared. Ductal carcinoma in situ was present significantly more often in the group with a primary recurring tumour, than in the matched group (P less than 0.001), and the same holds for lobular carcinoma (n = 5). Half of the tumours that recurred had macroscopically positive surgical margins compared to about one-fourth of the matched group. Fifty-six per cent of the DNA-aneuploid stemlines in cases with local recurrence were present in the corresponding primary tumour as well (confidence limits 45%-75%), an indication that the majority of local recurrences are true recurrences and not independently developed tumours. The lack of similarity of DNA stemlines between some primary DNA-aneuploid tumours and their local recurrences indicates that these tumours had developed independently. The percentage of DNA-aneuploid cases in the group with local recurrence (89%) did not differ significantly from that in the matched group (70%). However, the findings suggest a selective recurrence of DNA-diploid stemlines. This might indicate increased resistance of DNA-diploid tumour cells to radiotherapy as compared with the resistance level in DNA-aneuploid cells.     

Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases

PurposeDuctal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival.Patients and methodsThis study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS + RT), presenting local recurrences, with a 156-month median follow-up.ResultsEighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P = 0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P < 0.0007).ConclusionInvasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.     

Pathologic features related to local recurrence following lumpectomy and irradiation.

Breast conservation (lumpectomy and irradiation) has grown increasingly popular as a primary therapy for breast cancer. For the majority of patients whose breast cancers are now being detected at T1N0, both the expected cosmetic result and the survival are excellent. For this reason the possibility of local recurrences in the breast has a disproportionally larger impact on treatment planning for these patients. Although the majority of local recurrences occur in the vicinity of the primary tumor site within the initial 5 years of irradiation, local recurrences can be expected to occur well into the second decade as follow-up is continued. The majority of these late recurrences will not be in the immediate vicinity of the prior excision but represent de novo breast cancers developing in a multicentric fashion in other quadrants. Factors which influence recurrence per se include the size, grade, and stage (nodal status) of the tumor. Such factors influence local, locoregional, and distant metastases. A number of pathologic factors appear to affect only local recurrences. These, including positive margins, gross multicentricity, extensive intraductal carcinoma, and invasive lobular carcinoma, all share a common feature of a greater likelihood of local residual tumor burden. The increased risk of local recurrences related to positive surgical margins and extensive intraductal carcinoma can largely be eliminated by increasing the volume of tissue excised or the radiation dose. In summary, there are no absolute contraindications based on pathologic features of the tumor or the state of the resection margins which should preclude consideration of breast conservation for an individual patient.     

5-Year follow-up of sentinel node negative breast cancer patients.

AIM: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients. METHODS: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated. RESULTS: After a mean follow-up of 65 months (50-79) axillary recurrences were observed in four patients, local recurrences or ipsilateral second primary tumours were diagnosed in another seven patients. All axillary recurrences were diagnosed because of a palpable axillary mass; ultrasound in combination with fine needle aspiration cytology did not have an added value. CONCLUSION: It can be concluded that the incidence of axillary recurrences after negative SN is much lower than expected. There is no added value of US and FNAC of the axilla in the routine follow-up of SN negative patients.     

Personnalisation de la dose,du volume et du fractionnement de la radiothérapie du sein

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had “overtreatment” or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.     

Gene expression profiles of primary breast carcinomas from patients at high risk for local recurrence after breast-conserving therapy.

PURPOSE: Several risk factors for local recurrence of breast cancer after breast-conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also in improving understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. EXPERIMENTAL DESIGN: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients, 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9 of 19 patients, the local recurrence was also available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. RESULTS: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. CONCLUSIONS: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after BCT were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy.     

Predicting a local recurrence after breast-conserving therapy by gene expression profiling

Introduction

To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.

Methods

By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.

Results

Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.

Conclusion

Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.     

Location of pelvic recurrence after «curative» low anterior resection for rectal cancer

AIMS: It has been emphasized that the mesorectum is the key to local recurrence after resection for rectal cancer. In view of this we studied the location of recurrences, relative to the bed of the primary tumour, the neorectum and the level of anastomoses, in patients referred for recurrences after low anterior resection (LAR) in the . METHODS: The relative level above the anal verge of the primary cancer, the anastomosis and the recurrence was registered by proctoscopy in 46 patients operated on for recurrent cancer after low anterior resection. The origin of the recurrence was determined from the operative specimen. RESULTS: The median level of the primary cancers was 10 cm above the anal verge, with the anastomoses 2 cm lower, the majority being within 2 cm. Most recurrences were within 1 cm of the anastomosis. No rectal cancer occurred more than 3 cm distal to the anastomosis. Seventy to 80% of recurrences started peri-rectally, most invading the anastomosis. CONCLUSIONS: The tumour bed is most often the origin of the recurrence. Recurrences were mostly due to inadequate radial, and in a few cases longitudinal, dissection of the mesorectum. Virtually all recurrences were within reach of the examining finger. At follow-up of rectal cancers most local recurrences can therefore be identified earlier by digital examination than by proctoscopy.     

The hydra phenomenon of cancer: why tumors recur locally after microscopically complete resection

After surgical resection with microscopically clear margins, solid malignant tumors recur locally in up to 50%. Although the effect of a local tumor recurrence on the overall survival may be low in common cancers such as carcinoma of the breast or prostate, the affected patients suffer from exacerbated fear and the burden of the secondary treatment. With some tumor entities such as carcinoma of the uterine cervix or carcinoma of the head and neck, a local recurrence indicates incurability in the majority of cases. The pathomechanisms of local tumor spread and relapse formation are still unclear and comparatively little research has been devoted to their elucidation. Through the analysis of clinical and molecular data, we propose the concept of two pathogenetically and prognostically different local relapse types (i) in situ recurrences that arise in the residual organ/organ system not involved in the surgery for the primary tumor and (ii) scar recurrences that develop at the site of previous tumor resection. Whereas field cancerization, the monoclonal or multiclonal displacement of normal epithelium by a genetically altered but microscopically undistinguishable homologue, may explain the origin of in situ recurrences, most scar recurrences are regarded as the result of the interaction of minimal residual microscopically occult cancer with the surgical wound environment inside a developmentally defined tissue or organ compartment. The therapeutic implications derived from these concepts and areas of future research aimed to reduce local relapses are discussed in this perspective.     

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.     

Treatment of Recurrent Squamous Cell Carcinoma of the Vulva

Continuous follow-up of 244 patients treated for primary invasive squamous cell carcinoma of the vulva during a 20-year period (1960-1979) resulted in the detection of recurrent (or persistent) disease in 60 cases. Forty-one of these cases developed local or regional recurrence, or both, later than six months after treatment, and an analysis of the result of retreatment in this group is presented. Twenty-nine had local recurrences, nine regional metastases and three local recurrences and regional metastases. The treatment technique for local recurrences was surgery, in a few cases combined with irradiation and chemotherapy. In approximately one-third of the cases, this treatment resulted in long-term or permanent cure. In cases of regional metastases the prognosis was often extremely poor, but treatment normally gave good palliation although of short duration.     

Prognostic factors in patients undergoing curative irradiation for breast cancer

We have evaluated 147 patients who received primary curative irradiation for breast cancer to determine if there were any common factors that predisposed to failure. There were 10 local recurrences, for an overall local control rate of 93.2%, with a 2 to 16 year follow-up. Disease-free survivals were 85% in Stage I, 69% in Stage II, and 50% in Stage III. Age seemed to be a determinant, with a 31.6% local recurrence rate in women under 50 vs. a 3.1% rate of local recurrence in women age 50 or older when treated. We have also noted a correlation between the radiation dose and local recurrence, with a recurrence rate of 9.1% following a dose of 6000 rad or less, vs. a rate of 4.7% with a dose of 6400 rad or more. The size of the primary carcinoma and the status of the axillary lymph nodes, each considered individually, were not significant prognostic factors. There was no relationship between recurrence and the performance of an axillary dissection. There was evidence suggesting that the recurrence rate was lower when a wide local excision was performed, compared to a lesser procedure. Multiple foci of carcinoma and a high nuclear grade appear to have a poor prognosis. Five of the recurrences occurred early (under 2 years) and three of these were accompanied by fatal distant metastases. None of the five patients with late recurrences (37 to 116 months) developed metastatic disease, suggesting that late recurrences may have a better prognosis.     

Fusion imaging to evaluate the radiographic anatomical relationship between primary tumors and local recurrences in retroperitoneal soft tissue sarcoma

BackgroundLocal recurrence (LR) of retroperitoneal soft tissue sarcoma (RPS) is a common and life-threatening event. The evaluation of the exact anatomical patterns of local recurrence might help to improve local treatment in RPS.MethodsOf our local database we extracted ten patients with LR of RPS with axial MRI and/or CT datasets of the primary tumor (PT) and the LR. Using the Osirix DICOM viewer Version v.3.9.4 64-bit (Pixmeo, Geneva, Switzerland) we performed a three-step fusion algorithm consisting of: a) 3-point co-registration of the axial datasets depicting the PT and the LR using three abdominal landmarks b) re-orientation of the datasets and c) image fusion. We evaluated the feasibility of this technique with regard to categorizing the localization of LR as within or distant from the PT.ResultsFusion imaging was feasible in seven out of ten patients. In the other three patients anatomical shifting of organs after surgery led to a relevant mismatch of anatomical landmarks and impeded interpretation of the fused images. In five of seven patients with successful fusion imaging, local recurrences were located within the anatomical borders of the primary tumor, in two out of seven patients local recurrences were distant to the primary.ConclusionsFusion imaging of primary tumors and local recurrences is feasible in most patients with RPS. Most local recurrences occurred within the anatomical localization of the primary tumor. For further investigations validation of the technique in larger patient cohorts is required.