Risk Of Local Recurrence In Patients Research Articles

Survival and Local Recurrence Risk in Patients with High-Risk Neuroblastoma Treated with Proton Therapy over a 10 Year Interval

Patients (pts) with high-risk neuroblastoma (HR-NBL) require radiation (RT) to the primary tumor site (PS); approach is standardized within North American paradigms but remains a subject of global study. Long-term experience using proton therapy (PRT) in this population is lacking. We hypothesized that PRT would be associated with low risk of local recurrence (LR) in a large population of pts with HR-NBL spanning > 10 years. Sequential pts with HR-NBL at a single institution received RT to PS and persistent metastatic sites (MS). Dose to PS after subtotal resection (STR) was reduced from 36 Gy to 21.6 Gy in 2019 based on results from the Children's Oncology Group ANBL0532 trial (Liu K, 2019). Analysis using Kaplan Meier method and log rank test was performed with IRB approval. From 9/2010 - 12/2021, 99 pts with HR-NBL received PS RT during first-line therapy; most [78, (79%)] had adrenal primary tumors and 26 (26%) received MS RT. Median age was 48m at RT (R 11m to 17.5y) and 52 (53%) were female. All pts had multi-agent induction chemotherapy (CT) [+ dinutuximab [12 (13%)] and/ or therapeutic 131MIBG [19 (19%)] and resection of primary tumor prior to RT; 34 (34%) patients had STR with residual disease (RD) on post-op imaging, 65 (66%) had gross total resection (GTR). Dose to PS was 21.6 Gy for 78 (79%) pts and 36 Gy for 21 (21%) based on RD and treatment era; PRT was pencil beam [78 (79%)] or double scattered [22 (22%)], combined with IMRT in 2 (2%). With median FU of 4.2 yrs (R 0.5y - 12y), 80 pts (81%) are alive [66 (67%) disease-free, 14 (14%) with disease], 19 (19%) have died. Progressive disease (PD) occurred in 33 (33%), with median time to PD 24m (R 8-116m); two pts (2%) had isolated LR, 25 (25%) distant PD, and 6 (6%) concurrent LR and distant PD. Risk of LR at 10 years was 8%; absolute risk of any LR was 8% (6/78) in 21.6 Gy cohort and 9% (2/21) in 36 Gy cohort (p = NS). After induction CT, 34 (34%) pts had STR with > 1cm3 RD on axial imaging; 18/ 34 (53%) also had MIBG uptake (MIBG+) at PS. Based on treatment era, 21 pts (62%) after STR received 21.6 Gy + boost to RD (36 Gy), and 13 (38%) 21.6 alone. Of those who received 36 Gy (median FU 5.7y), 2/21 (9.5%) had LR with concurrent distant PD; of those who received 21.6 Gy (median FU 3.2y) 4/13 (31%) had LR (2 with concurrent distant PD and 2 LR only) (p = 0.03). In the 21.6 Gy GTR cohort, 2/65 (3%) had LR + distant PD. Of 8 total patients who experienced LR, 5 had MIBG + RD, 1 MIBG- RD, and 2 GTR. We observed excellent outcomes in 99 pts treated with proton radiotherapy for HR-NBL from 2010 through 2021, with 81% of patients alive and 92% free of LR. Our data suggest that LR is rare after GTR and 21.6 Gy, and uncommon among pts with STR treated with 36 Gy. A small number of pts received 21.6 Gy after STR, however, this experience suggests that a subset of pts with RD may require RT dose > 21.6 Gy. Further work is required to further characterize individual management of PS in pts with HR-NBL with regard to extent of RD and biologic disease features.

780 Effectiveness of Colonic/Rectal Washout in Reducing Risk of Local Recurrence in Rectal and Distal Left Sided Colonic Cancer Resection. A Meta-Analysis

Abstract Background Lab and clinical studies have shown evidence that local recurrence (LR) occurs due to free cancer cells at resection sites. Evidence for the effectiveness of rectal washout (RW) in washing out these cells and reducing the incidence of local recurrence in the literature is equivocal. Aims To determine whether intraoperative RW can effectively reduce the incidence of LR in rectal and distal colonic tumour resection. Method A literature search was conducted according to PRISMA guidelines. The primary endpoint was incidence of local recurrence of cancer after rectal cancer surgery. Results The meta-analysis revealed that at 5 year follow up, local recurrence in the washout group (WO) was 6.08% compared to 9.48% in the no-washout group (NWO) group (OR 0.63, 95% CI = 0.51 –0.73, Chi2 = 6.76, df = 7, p = 0.45). Based on this study we found the number needed to treat would be 29.3 (95%CI 20.9 –56.6) in order to prevent one local recurrence at 5 years. Conclusions RW reduces the risk of LR in patients with distal colorectal cancer resection in the long term follow up. A small number of patients needed to be treated to avoid one local recurrence in the five year follow up.

Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls.

Denosumab is a monoclonal antibody against RANK ligand for treatment of giant cell tumor of bone (GCTB). Clinical trials and case series have demonstrated that denosumab is relevant to beneficial tumor response and surgical down-staging in patients of GCTB. However, these trials or case series have limitations with a short follow-up. Recent increasing studies revealed that denosumab probably increased the local recurrence risk in patients treated with curettage. This may be caused by the thicken bone margin of tumor that trapped tumor cells from curettage. The direct bone formation by tumor cells in the margin after denosumab treatment also contributed to the local recurrence. in vitro studies showed denosumab resulted in a cytostatic instead of a true cytotoxic response on neoplastic stromal cells. More importantly, denosumab-treated GCTB exhibited morphologic overlap with malignancy, and a growing number of patients of malignant transformation of GCTB during denosumab treatment have been reported. The optimal duration, long term safety, maintenance dose, and optimum indications remain to be elucidated. With these concerns in mind, this review warns that the denosumab therapy of GCTB should be applied with caution.

The adequacy of resection margin for non-infiltrative soft-tissue sarcomas

ObjectivesThere remains no consensus on what constitutes an adequate margin of resection for non-infiltrative soft-tissue sarcomas (STSs). We aimed to investigate the role of resection margins in millimetres for non-infiltrative STSs. Methods502 patients who underwent surgical resection for a localized, non-infiltrative, high-grade STSs were studied. The prognostic significance of margin width was analysed and compared with the conventional R- and R+1-classification of surgical margins. ResultsThe overall local recurrence (LR) rate was 13%; 9% and 27% with negative and positive margins, respectively (p < 0.001). In patients with negative margins, the LR rates were greater than 10% in patients with margins ≤5.0 mm but reduced to less than 4% with margins >5.0 mm. When classified by the R- (or R+1)-classification, the 5-year cumulative LR incidence was 8%, 23% (16%), and 31% for R0, R1, and R2, respectively, which did not stratify the LR risk with negative margins. On the other hand, an accurate risk stratification was possible by metric distance; the 5-year cumulative incidence of LR was 29%, 10%, and 1% with 0 mm, 0.1–5.0 mm, and >5.0 mm, respectively (p < 0.001). This classification also stratified the LR risk in patients with or without adjuvant radiotherapy. ConclusionWhile a negative margin is essential to optimize local control in patients with non-infiltrative STSs, surgical margin width greater than 5 mm minimises the risk of local failure regardless of the use of adjuvant radiotherapy.

Update on indications for lateral lymph node dissection in the management of lower rectal cancer.

The presence of lateral lymph node (LLN) metastasis was associated with higher local recurrence risk in patients with lower rectal cancer. The role of LLN dissection has not been fully determined despite prolonged debate that last for few decades. The practical difference between Japan and the West was the main culprit. Japanese used to rely on surgical removal of LLN as local control while the West believed that LLN dissection could be spared after giving neoadjuvant chemoradiotherapy. As time passed, it is getting more common to combine both treatments. With the quality improvement in magnetic resonance imaging, we can now predict the chance of LLN metastasis and evaluate the treatment response with good accuracy. Few large analyses have been published recently and provided us more insight into this topic. In this review, we summarized and provided an update on the latest evidence. We have proposed a treatment algorithm on the management of LLNs which may help clinical decision and provide idea for further research.

Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.

Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established. (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage? We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis. The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group. The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

What is an adequate margin for infiltrative soft-tissue sarcomas?

ObjectivesWhat constitutes an adequate margin of resection for infiltrative subtypes of soft-tissue sarcomas remains unclear. We aimed to determine the prognostic significance of the margin in millimetres for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods305 patients diagnosed with either a high-grade, localised MFS (n = 98) or UPS (n = 207) were included. The relationship of closest margin in millimetres to viable tumour and oncological outcomes was analysed. ResultsThe overall local recurrence (LR) rate for all patients were 12%: 19% with positive margin and 10% with negative margin (p = 0.051). The LR rate was similar in patients with negative but <10 mm margin; 13%, 6%, 15%, 17% with 0.1–0.9 mm, 1.0–1.9 mm, 2.0–4.9 mm, and 5.0–9.9 mm margin, respectively. However, the LR rate decreased to 3% if the margin was ≥10 mm. By the R- or R+1-classification, the 10-year cumulative probability of LR was 9%, 15%, 48% for R0, R1, R2 resections, respectively, which was not sensitive enough to stratify the LR risk in patients with negative margins. However, the cumulative probability of LR was significantly stratified by metric distance; the 10-year cumulative LR probability was 3%, 14%, 25% with ≥10.0 mm, 0.1–9.9 mm, and 0 mm, respectively (p = 0.026). A trend towards improved local control by adjuvant radiotherapy was seen in patients with 0–9.9 mm margin (p = 0.078). ConclusionThe resection margin, when measured as a metric distance, correlates with a reduction in LR, and appears to be more significant on local control than radiotherapy. To minimise the risk of LR, a margin distance of at least 10 mm is advocated for MFS and UPS.

Is there a need for neoadjuvant short-course radiotherapy in T3 rectal cancer with positive lymph node involvement? A single-center retrospective cohort study

BackgroundNeoadjuvant short-course radiotherapy is used to reduce local recurrences in stage III rectal cancer. Radiotherapy is not harmless, and meticulous total mesorectal excision surgery alone has been reported to result in low local recurrence rate in favorable stage III tumors. The aim was to evaluate the effect of short-course (5 × 5 Gy) radiotherapy on the local recurrence risk in patients with pT3N1-2 rectal cancer.Materials and methodsThis was a retrospective study with 151 consecutive pT3N1-2M0 rectal cancer patients operated on at Helsinki University Hospital, Helsinki, Finland, during January 2005 to June 2014. Short-course radiotherapy was given to 94 patients, and 57 patients were operated on without neoadjuvant radiotherapy. The main outcome measurement was the effect of radiotherapy on local recurrence. Also, the risk factors for local recurrence were analyzed.ResultsLocal recurrence occurred in a total 17 of 151 (11.3%) patients, 8 of 57 (14.0%) in surgery only group compared with 9 of 94 (9.6%) in radiotherapy plus surgery group (p = 0.44). In univariate Cox regression analysis, the risk factors for local recurrence were tumor location under 6 cm from the anal verge (p = 0.01), involved lateral margin (p < 0.001), tumor perforation (p < 0.001), and mucinous histology (p = 0.006). In multivariate analysis, risk factors were tumor location under 6 cm from anal verge (p = 0.03) and involved lateral margin (p = 0.002).ConclusionNeoadjuvant short-course radiotherapy did not affect the local recurrence risk of pT3N1-2M0 rectal cancer. Further studies with larger patient number are needed to evaluate the role of short-course radiotherapy in different T3 subgroups (3a–c) as well as in N1 and N2 cancers in separate.

Correlation of histopathologic features of ductal carcinoma in situ of the breast with the oncotype DX DCIS score

The Oncotype DX Breast Cancer Assay for ductal carcinoma in situ is used to determine local recurrence risk in patients with ductal carcinoma in situ. The results help select patients with low-risk ductal carcinoma in situ who could forgo radiation therapy after conservative surgery. The genes assessed include five proliferation genes, progesterone receptor (PR), and GSTM-1. Our objective was to determine if PR, mitotic counting, or any other pathologic feature of ductal carcinoma in situ could predict the Oncotype DX DCIS Score. We identified 46 cases of ductal carcinoma in situ with a Oncotype DX DCIS Score. In addition to information obtained from routine pathology, we counted mitotic figures in the ductal carcinoma in situ and noted presence of dense chronic inflammatory infiltrate surrounding ductal carcinoma in situ. We found that PR ≥90% (P=0.004), mitotic count ≤1 (P=0.045), estrogen receptor ≥90% (P=0.046), and low nuclear grade (P<0.0001) were associated with a low score. Dense chronic inflammation surrounding ductal carcinoma in situ was associated with a high score (P=0.034).All 13 cases with PR ≥90%, ≤1 mitotic figure and absence of dense chronic inflammation around ductal carcinoma in situ had a low score (100% specificity). A low score was not observed in any case with at least two of the following—negative PR, >1 mitotic figure, and/or presence of dense chronic inflammation around ductal carcinoma in situ (100% specificity). Our study suggests using a combination of PR (≥90% vs negative) with mitotic count in ductal carcinoma in situ (≤1 vs >1) and dense chronic inflammation around ductal carcinoma in situ one could predict the Oncotype DX DCIS score. Mitotic counting and evaluation of immune response might provide prognostic information in ductal carcinoma in situ.

Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis

The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23-0.64]. The absolute risk difference was 10.1% (95% CI: 4.9-17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: -0.10-0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: -0.28-1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS.

Regenerative therapy with mesenchymal stem cells at the site of malignant primary bone tumour resection: what are the risks of early or late local recurrence?

There is concern that regenerative cell-based therapies at the site of malignant primary bone tumours could result in increased risk of local tumour recurrence. We therefore investigated the long-term risks for site-specific recurrences in patients who had received an autologous bone marrow derived mesenchymal stem cell suspension to improve healing at the host-to-allograft bone junction of the reconstruction after bone tumour resection. A total of 92 patients were treated from 1993 to 2003 with bone marrow-derived mesenchymal stem cells after bone tumour resection. Patients were monitored for cancer incidence from the date of first operation (1993) until death, or until 31 December 2013. The mean follow-up time was 15.4 years (range ten to 20 years). The average number of MSCs returned to the patient was 234,000 MSCs ± 215,000. The primary outcome was to evaluate the risk of tumorigenesis recurrence at the cell therapy treatment sites with radiographs and/or MRIs. The relative risk of cancer recurrence was expressed as the ratio of observed and expected number of cases according to three different control populations. Thirteen recurrences were found at the treatment sites among the 92 patients. The expected number of recurrences based on incidence in the three cohort populations was between 15 and 20 for the same cancer, age and sex distribution. The standardized incidence ratio (equal to observed cancers divided by expected cancers) for the entire follow-up period and for all recurrences was between 0.65 and 0.86 (95 % CI 0.60-1.20). This study found no increased cancer local recurrence risk in patients after application of autologous cell-based therapy using bone marrow-derived mesenchymal stem cells at the treatment site after an average follow-up period of 15.4 years, ranging from ten to 20 years.

Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS)

Whether wide excision with margins ≥1cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent ≤2.5cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins ≥1cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11years. Nineteen patients (13%) had LR as a first event within 8years. Thirteen LR (68%) were DCIS only and six (32%) were invasive. Fourteen (74%) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6%. The estimated annual percentage rate of LR was 1.9% per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation.

The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

Hypofractionated Whole Breast Radiation in Women with DCIS or Grade 3 Invasive Breast Cancer

Randomized data supports hypofractionated whole breast radiation as an appropriate, cost-effective approach demonstrating similar local control, survival, and cosmesis when compared with conventional fractionation. Data is relatively scarce regarding management of DCIS with hypofractionated radiation. Recent randomized data also point to local recurrence risk in patients with invasive grade 3 tumors as a potential concern. We review a large, single-institution experience in using hypofractionated radiation to the intact breast, focusing on outcomes in patients with DCIS or grade 3 invasive breast cancer.

MMP7 Gene Polymorphism Associated with Increased Local Recurrence Risk in Patients Receiving Radical Prostatectomy for Early-stage Prostate Cancer: Implications for Postoperative Radiation Therapy

MMP7 Gene Polymorphism Associated with Increased Local Recurrence Risk in Patients Receiving Radical Prostatectomy for Early-stage Prostate Cancer: Implications for Postoperative Radiation Therapy

The Effect of Delaying Adjuvant Radiation Treatment after Conservative Surgery for Early Breast Cancer

We examined the effect of delaying radiation treatment after conservative surgery on the risk of breast cancer local recurrence (LR). From January 1997 to December 2001, 969 women with early-stage breast cancer were treated at the Radiation Oncology Department in Chieti. We analyzed 802 of them who underwent conservative surgery followed by whole-breast radiotherapy. The patients were divided into two groups: women who did not receive chemotherapy and women who received chemotherapy. The time intervals from surgery to breast irradiation used for the analysis were <16 or more weeks for no-chemotherapy-treated women, and <25 and 25 or more weeks for chemotherapy-treated women. The relationship between LR and factors such as age, tumor size, margin status, and surgery-radiotherapy time interval was evaluated. The 8-year LR risk was estimated using the Kaplan-Meier method. LR was observed in 33 (4.1%) of the 802 patients. The overall 8-year LR risk was 6.5% (+/-1.51). In the no-chemotherapy group, the risk of LR was associated with a younger age and a positive margin status. In the chemotherapy group LR was associated with a younger age and a tumor size >3 cm. Surgery-radiotherapy interval was not associated with LR in both groups of patients. Delay in the start of radiotherapy does not increase the risk of LR in patients with early breast cancer treated or not treated with chemotherapy.

Transanal Endoscopic Microsurgical Excision of pT2 Rectal Cancer: Results and Possible Indications

In previous studies, local excision was predominantly established for "low-risk" pT1 rectal cancer. The results obtained with T2 tumors are unclear; recurrence rates of 0 to 67 percent were reported. This study was designed to determine the value of local excision for T2 rectal carcinomas, prognostic factors, and the need for reoperation. After local excision of 649 patients with rectal tumors, pT2 carcinoma was found in 44 patients. In general, immediate reoperation was recommended; however, 24 patients declined further surgery or were not reoperated because of comorbidities. The results were analyzed separately for local R0 resection of low-risk carcinomas and for prognostically unfavorable criteria (R1/RX/R < or = 1mm/G3-4/L1/V1). Reoperation was performed within four weeks. Recurrences also were divided by previous local R0 resection of low-risk tumors as well as by unfavorable results and were analyzed in a long-term, follow-up study. Patients with palliative therapy were excluded, and follow-up was obtained in 90 percent (20 transanal endoscopic microsurgical excision alone, 17 transanal endoscopic microsurgical excision and reoperation). Local recurrence rates after local R0 resection alone of low-risk T2 carcinomas were 29 percent, whereas patients with unfavorable criteria developed recurrences in 50 percent. After immediate reoperation, the local recurrence risk in patients without lymph node filiae was significantly reduced to 7 percent. Local R0 resection of low-risk pT2 carcinomas represents an inadequate therapy. In pT2N0M0 rectal carcinomas, the recurrence rate can be reduced through immediate reoperation to a level similar to primary radical surgery. An initial poor local resection result (R1/RX/R < or = 1 mm/G3-4/L1/V1) has no negative influence on further oncologic outcome.

Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer

To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (> or =1 cm), close (>0 and <1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects.

Family history of breast cancer and local recurrence after breast-conserving therapy

The impact of a family history of breast cancer on the local recurrence (LR) risk after breast-conserving therapy (BCT) was performed within the framework of a large, multicentre matched case–control study of risk factors for LR after BCT (BORST study). Family history was assessed for 218 breast cancer patients with LR (cases) and 480 patients without LR (controls). Detailed histological tumour features were determined by review of the primary tumour. The risk of LR for patients with a positive family history was similar to or less than that of non-familial patients (unadjusted odds ratio (OR unadj) 0.66 (95% confidence interval (CI) 0.40–1.08)). Familial patients were older than non-familial patients ( P=0.07) and their tumours had a lower histological grade ( P=0.07). A second primary tumour occurred significantly more often in familial patients ( P=0.02). Adjustment for these factors did not essentially alter the results (OR adj 0.71 (0.38–1.32)). Separate analyses according to age at onset (younger and older than 50 years) and time to LR/site of LR produced similar results. The sole presence of a positive family history of breast cancer does not appear to be a risk factor for local recurrence after BCT. Whilst this might be different for genetically predisposed patients, a positive family history does not appear to be a contra-indication for BCT.

The role of radiation therapy in the management of primary breast cancer

The role of radiation therapy in the management of primary breast cancer