5-year Local Recurrence-free Survival Research Articles

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy

BackgroundIn breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR.MethodsThis was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival.ResultsOf the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74–1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups.ConclusionIBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Long-term survival, toxicities, and the role of chrono-chemotherapy with different infusion rates in locally advanced nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy: a retrospective study with a 5-year follow-up.

This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.

Oncologic safety of breast conserving surgery after neoadjuvant chemotherapy in patients with multiple ipsilateral breast cancer: A retrospective multi-institutional cohort study

IntroductionThe recent ACOSOG Z11102 trial demonstrated low recurrence rates with breast conserving surgery (BCS) in women with multiple ipsilateral breast cancers (MIBC). Questions remain regarding the oncologic safety of BCS in women with MIBC receiving neoadjuvant chemotherapy (NAC). MethodsWe conducted a retrospective cohort study of adult patients who underwent BCS following NAC for stage I-III breast cancer from 2012 to 2021 at two academic centers. Descriptive statistics were used to summarize the data and the Kaplan-Meier method was used to provide estimates for recurrence and survival outcomes. MIBC was defined as ≥2 foci of malignancy. ResultsA total of 544 patients were included; 29.4% (n = 160) ER+/HER2-, 17.7% (n = 96) ER+/HER2+, 18.2% (n = 99) ER-/HER2+, and 34.7% (n = 189) with ER-/HER2-disease. Overall, 80.5% (n = 438) had unifocal breast cancer while 19.5% (n = 106) had MIBC. Of patients with MIBC, 90.6% (n = 96) had multifocal and 9.4% (n = 10) had multicentric disease. Pathologic complete response was achieved in 41.1% of patients with MIBC versus 41.5% of patients with unifocal disease (p = 0.94). At a median follow-up of 55 months (IQR 32-83); 4.8% of patients in the unifocal group and 4.7% of patients in the MIBC group had had a local recurrence (p = 0.97). There was no difference in 5-year local recurrence-free survival (p = 0.92), recurrence-free survival (p = 0.06), or overall survival (p = 0.07) between the groups. ConclusionIn this large cohort of women undergoing BCS post-NAC, there was no significant difference in in breast tumor recurrence or survival outcomes between patients with unifocal disease and those with MIBC.

En Bloc Surgery in the Thoracic Spine: Indications, Results, and Complications in a Series of Eighty-Five Patients Affected by Primary and Secondary Malignant Bone Tumors

BackgroundEn-bloc resection remains the cornerstone treatment for malignant bone tumors affecting the spine. The thoracic spine poses unique challenges due to the proximity of crucial structures. This study assesses outcomes of patients who underwent en-bloc spondylectomy for malignant bone tumors at the thoracic level. MethodsWe retrospectively reviewed 85 cases of primary and secondary bone tumors in the thoracic spine, undergoing en-bloc spondylectomy from 1996 to 2016. Evaluation encompassed clinical presentation, tumor characteristics, surgical outcomes, complications, survival rates, and recurrence. ResultsOf 85 patients, 40 presented directly, while 45 had undergone prior intralesional surgery. Chondrosarcoma and chordoma comprised the most prevalent primary histological types; thyroid and kidney carcinomas were the most frequent secondary tumors. Pain was reported in 75 patients at diagnosis. Margins were adequate in 54 cases and intralesional in 31. Immediate postoperative deaths amounted to four. Major complications included substantial blood loss, neurological deterioration, and paraplegia. The 5-year Local Recurrence-Free Survival rate was 58.7%, significantly influenced by the surgical margin: patients with wide margins experienced a 5-year LRFS of 85.7%, while those with marginal and intralesional margins had rates of 56.7% and 45.6%, respectively; overall recurrence was 22.3% with no notable disparities between previously treated and untreated patients. The 5-year Overall Survival (OS) rates were 63.2% and 56.2% for primary and secondary tumors, respectively. The OS was not significantly influenced by surgical margins. ConclusionsManaging malignant thoracic bone tumors poses significant challenges. This study underscores the criticality of achieving adequate margins, particularly following previous intralesional approaches.

The individualized delineation of clinical target volume for primary nasopharyngeal carcinoma based on invasion risk of substructures: A prospective, real-world study with a large population

Background and purposeThe delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. Materials and MethodsWe preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 ∼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. ResultsFrom January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1–126.9) and 51.4 (39.5–78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5–98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. ConclusionOur individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.

Comparison of long-term oncological outcomes after central lumpectomy versus nipple-sparing breast-conserving surgery for centrally located breast cancer: a propensity score-matched study.

To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.

Identification of predictors for short-term recurrence: comprehensive analysis of 296 retroperitoneal liposarcoma cases

BackgroundThe short-term (≤ 1 year) recurrence (STR) is the primary determinant impacting both the life quality and survival duration in patients who have undergone surgical resection for retroperitoneal liposarcoma (RPLS), a condition with intricate and ambiguous pathogenesis. The purpose of this study was to analyze the risk factors associated with STR in cases of RPLS and primary retroperitoneal liposarcoma (PRPLS).MethodsFor this retrospective observational study, a total of 296 RPLS cases were selected as research subjects, who experienced tumor recurrence during the follow-up period. The Local recurrence-free survival (LRFS) rates were estimated using the Kaplan–Meier method and subsequently compared between groups utilizing the log-rank test. The subsequent analyses involved univariate and multivariate logistic regression to identify predictors of STR in RPLS cases. Additionally, a logistic regression model was constructed for PRPLS.ResultsThe 1-, 3-, and 5-year LRFS rates of the 296 RPLS cases were 51.7%, 16.9%, and 7.1%, respectively. In the univariate analysis, several factors were found to be associated with STR, including preoperative neutrophil/lymphocyte ratio (NLR), smoking history, surgical frequency, combined organ excision, operative time, intraoperative bleeding, transfer to the intensive care unit (ICU), multiple primary tumors, tumor shape and capsule characteristics, histological subtype, and presence of tumor necrosis. The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, and tumor necrosis were identified as independent risk factors for STR in surgically resected RPLS. Conversely, diabetes, intact tumor capsule, and well-differentiated histological subtype appeared to be independent protective factors. Analysis for PRPLS revealed that tumor capsule and tumor necrosis were independent predictors of STR.ConclusionsThe elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, tumor necrosis, and tumor capsule were expected to serve as predictive factors of STR for surgical resected RPLS and PRPLS.

Is Robotic Surgery Beneficial for Rectal Cancer Patients with Unfavorable Characteristic After Neoadjuvant Chemoradiotherapy?

The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.

Omission of radiotherapy to lymph node level III in patients with cN0 adenoid cystic carcinoma of the major salivary gland: a single center experience.

Due to the rarity of adenoid cystic carcinoma (ACC) of the major salivary gland, there is no consensus on the extent of prophylactic neck irradiation (PNI) for patients with clinically negative lymph nodes (cN0) disease. We conducted a retrospective analysis of all patients with ACC of the major salivary gland who received treatment at our center between January 2010 and April 2020. The primary endpoint was regional failure-free survival(RRFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and acute toxicity. A total of 139 patients were included in the analysis. For cN0 patients, the 5-year RRFS, OS, DMFS, and LRFS were 93.2%, 90.2%, 75.7%, and 91.4%, respectively. Multivariate analysis revealed that PORT was an independent prognostic factor for RRFS and LRFS. No statistically significant differences were observed between the Level III sparing PNI group and the Standard PNI group in terms of RRFS, OS, DMFS, and LRFS. The doses delivered to the larynx and thyroid in the Level III sparing PNI group were significantly lower than those in the Standard PNI group. In patients with cN0 ACC of the major salivary gland, PNI improves regional control, and the level III nodal region sparing radiotherapy does not increase the risk of level III recurrence, while potentially reducing toxicity.

Is radiotherapy necessary for upper rectal cancer underwent curative resection? A retrospective study of 363 patients

BackgroundTo investigate the impact of radiotherapy (RT) on recurrence and survival in patients with locally advanced upper rectal cancer underwent curative resection.Methods363 locally advanced upper rectal cancer cases were identified from the database of our hospital from 2010 to 2018. All patients underwent curative resection and had the lower margin of the tumor located 10–15 cm from the anal verge, among them, 69 patients received pre- or post-operative radiotherapy and 294 patients without. Local control and survivals were compared, and stratification grouping based on European Society for Medical Oncology risk factors were further compared. 1:2 propensity score matching analysis was used to reduce the impact of confounding factors.ResultsThere were 207 patients after 1:2 matching (RT group:non-RT group = 69:138). The 5-year overall survival (OS) of the RT group and non-RT group after matching was 84.1% and 80.9%, respectively(P = 0.440); the 5-year local recurrence-free survival (LRFS) was 96.5% and 94.7%, respectively(P = 0.364); the 5-year distant metastasis-free survival (DMFS) was 76.8% and 76.9%, respectively(P = 0.531). Subgroup analysis showed that radiotherapy could not significantly improve the overall survival, local recurrence, and distant metastasis with or without poor prognostic features. In the high-risk subgroup, the 5-year OS was 76.9% and 79.6% for patients treated with radiotherapy and without (P = 0.798), LRFS was 94.8% and 94.2%, respectively (P = 0.605), DMFS 68.7% and 74.7%, respectively (P = 0.233).ConclusionsOur results suggest that radiotherapy could not improve local control and survival for locally advanced upper rectal cancer patients underwent curative resection, even in the cases with poor prognostic features.

Surgical margins and prognosis of borderline and malignant phyllodes tumors.

To investigate the optimal surgical margin and prognostic risk factors for borderline and malignant phyllodes tumors (PTs). A retrospective analysis was conducted on patients with borderline and malignant PTs at our hospital from 2011 to 2022. Univariate and multivariate Cox proportional hazard models were employed to analyze the effects of various variables on local recurrence-free survival (LRFS) and disease-free survival (DFS). This study comprised 150 patients, 85 classified as borderline and 65 as malignant. During a median follow-up of 66months (range: 3-146months), 34 cases (22.7%) experienced local recurrence, 9 cases (6.0%) exhibited distant metastasis, and 7 cases (4.7%) resulted in death. Irrespective of the histological subtypes, patients with surgical margins ≥ 1cm exhibit significantly higher 5-year LRFS and 5-year DFS rates compared to those with margins < 1cm. Among patients with initial margins < 1cm, LRFS (P = 0.004) and DFS (P = 0.003) were improved in patients reoperated to achieve margins ≥ 1cm. Surgical margin < 1cm (HR = 2.567, 95%CI 1.137-5.793, P = 0.023) and age < 45years (HR = 2.079, 95%CI 1.033-4.184, P = 0.040) were identified as independent risk factors for LRFS. Additionally, surgical margin < 1cm (HR = 3.074, 95%CI 1.622-5.826, P = 0.001) and tumor size > 5cm (HR = 2.719, 95%CI 1.307-5.656, P = 0.007) were determined to be independent risk factors for DFS. A negative surgical margin of at least 1cm (with secondary resection if necessary) should be achieved for borderline and malignant PTs. Tumor size > 5cm and age < 45years were predictive of recurrence, suggesting multiple therapy modalities may be considered for these high-risk patients.

Ten-year follow-up outcomes of limited resection trial for radiologically less-invasive lung cancer.

The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. Our patients, with a median age of 62years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5years after surgery.

Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three– positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Is perioperative chemotherapy effective in patients with localized myxoid liposarcoma?

This study aimed to compare the local recurrence, distant metastasis and disease-specific survival rates of patients with localized myxoid liposarcoma in the surgery and adjuvant chemotherapy group versus the surgery alone group. A total of 456 patients in the Japanese National Bone and Soft Tissue Tumour Registry database who had localized myxoid liposarcoma and underwent surgery and adjuvant chemotherapy or surgery alone between 2001 and 2019 were included in this retrospective study. The study adjusted for background differences between patients who underwent surgery and adjuvant chemotherapy (n=228) or surgery alone (n=228) using propensity score matching. Univariate analysis showed no significant difference in local recurrence rate between the two groups (5-year local recurrence-free survival: 98.6% [95% confidence interval: 95.9-99.6] vs. 94.0% [95% confidence interval: 89.7-96.6], P=0.052). Univariate analysis showed no difference in the incidence of distant metastases between the two groups (5-year distant metastasis-free survival: 80.5% [95% confidence interval: 73.9-85.8] vs. 75.1% [95% confidence interval: 67.7-81.2], P=0.508). Univariate analysis showed no difference in disease-specific survival between the two groups (5-year disease-specific survival: 92.6% [95% confidence interval: 86.1-96.2] vs. 93.2% [95% confidence interval: 87.6-96.4], P=0.804). In the high-risk group (n=203) with high-grade tumours and tumour size ≥10cm, there were no significant differences in the local recurrence, distant metastasis and disease-specific survival rates between the surgery and adjuvant chemotherapy group and the surgery alone group. The effect of adjuvant chemotherapy on localized myxoid liposarcoma appears to be limited.

Long-term efficacy of transanal local excision versus total mesorectal excision after neoadjuvant treatment for rectal cancer: A meta-analysis.

The purpose of this meta-analysis is to compare the long-term efficacy of transanal local excision (TLE) versus total mesorectal excision (TME) following neoadjuvant therapy for rectal cancer. The Web of Science, Pubmed, Medline, Embase, and the Cochrane Library were systematically searched for correlational research. The Newcastle-Ottawa Scale and the Cochrane risk of bias tool were used to assess the quality of cohort studies (CSs) and randomized controlled trials (RCTs), respectively. Statistically analyzed using RevMan5.4. A total of 13 studies, including 3 randomized controlled trials (RCTs) and 10 cohort studies (CSs), involving 1402 patients, were included in the analysis. Of these, 570 patients (40.66%) underwent TLE, while 832 patients (59.34%) underwent TME. In the meta-analysis of CSs, no significant difference was observed between the TLE group and TME group regarding 5-year overall survival (OS) and 5-year disease-free survival (DFS) (P > 0.05). However, the TLE group had a higher rates of local recurrence (LR) [risk ratio (RR) = 1.93, 95%CI (1.18, 3.14), P = 0.008] and a lower rates of 5-years local recurrence-free survival (LRFS) [hazard ratio (HR) = 2.79, 95%CI (1.04, 7.50), P = 0.04] compared to the TME group. In the meta-analysis of RCTs, there was no significant difference observed between the TLE group and TME group in terms of LR, 5-year OS, 5-year DFS, and 5-year disease-specific survival (P > 0.05). After undergoing neoadjuvant therapy, TLE may provide comparable 5-year OS and DFS to TME for rectal cancer. However, neoadjuvant therapy followed by TLE may has a higher LR and lower 5-year LRFS compared to neoadjuvant therapy followed by TME, so patients should be carefully selected. Neoadjuvant therapy followed by TLE may be a suitable option for patients who prioritize postoperative quality of life. However, the effectiveness of this approach requires further research to draw a definitive conclusion.

Predictive capacity of FAT1 transcriptional expression in patients with head and neck squamous cell carcinomas treated with radiotherapy

ObjectiveTo analyze the predictive capacity at the primary location of the tumor of the FAT1 transcriptional expression in patients with head and neck squamous cell carcinoma treated with radiotherapy. Material and methodsWe conducted a retrospective study from biopsies of the primary location of the tumor in 82 patients with head and neck squamous cell carcinoma treated with radiotherapy. The transcriptional expression of FAT1 was determined by RT-PCR. The level of FAT1 transcriptional expression was categorized according to the local control after radiotherapy using a recursive partitioning analysis. ResultsElevated FAT1 transcriptional expression was associated with an increased risk of local recurrence after radiotherapy. Patients with a high expression level of FAT1 (n=18; 22.0%) had a 5-year local recurrence-free survival of 42.1% (95% CI: 18.6%–65.6%), whereas for patients with a low expression (n=64; 78.0%) it was 72.4% (95% CI: 61.5%–83.3%) (p=0.002). According to the result of a multivariate analysis, patients with a high FAT1 expression category had a 2.3-fold increased risk of local recurrence (95% CI: 1.0–5.2; p=0.043). ConclusionsElevated FAT1 transcriptional expression was associated with a significantly increased risk of local recurrence in patients with head and neck squamous cell carcinoma treated with radiotherapy.

Salvage Abdominoperineal Resection for Locally Recurrent or Persistent Anal Squamous Cell Carcinoma after Definitive Chemoradiation.

Initial treatment for patients with squamous cell carcinoma of the anal canal includes definitive chemoradiation. Salvage abdominoperineal resection (APR) is the treatment of choice for recurrent or persistent disease. Older studies suggest approximately 50% successful salvage of recurrent or persistent disease with APR. Risk factors for failure after salvage APR are incompletely characterized. Using a single institutional database, patients were identified who underwent salvage APR after definitive intensity-modulated radiotherapy-based chemoradiation between 2003 and 2022. Clinical and pathologic variables analyzed included age at APR, sex, race, HIV status, initial cT stage, initial cN stage, radiation dose, recurrent vs persistent disease, recurrent pT stage, recurrent pN stage, the presence of LVSI, PNI or <2mm surgical margins, and the use of either intraoperative radiation or another treatment modality in addition to APR. The log rank test was used to determine differences in time from APR to events (local recurrence, distant metastasis and death) based on clinical and pathologic variables. The Cox Proportional Hazard Model was used to perform multivariable analysis for all factors with a univariate P-value <0.1. Of 628 patients with anal squamous cell carcinoma, 50 (8.0%) were treated with abdominoperineal resection for locally recurrent (n = 29, 58%) or locally persistent (n = 21, 42%) disease. Median [interquartile range] follow up was 40.0 months [15.2-68.0 months] from APR. Median local recurrence-free survival was not reached; 1- and 2-year local recurrence-free survival was 81% (95% CI 72-92%) and 76% (64-89%). On multivariable analysis, pathologic T-stage of the recurrence (3.85 (1.07-13.9); P = .040), the presence of lymphovascular space invasion (9.1 (1.12-73.62); P = .038) and surgical margins <2mm (8.81 (2.11-36.73); P = .003) were all significantly associated with higher rates of local recurrence. Median distant metastasis-free survival was not reached; 1- and 2-year distant metastasis-free survival was 88% (81-98%) and 79% (67-92%). On multivariable analysis, only persistent (versus recurrent) local disease was significantly associated with higher rates of distant metastasis (1.23 (1.05-5.55) P = .043). Median overall survival was not reached; 1- and 2-year overall survival was 90% (81-98%) and 78% (65-90%). On multivariable analysis, only recurrent pT stage (T3/4 vs T1/2) was associated with higher rates of death (5.87 (1.02-33.65); P = .047). APR is a successful salvage modality for anal squamous cell carcinoma with recurrent or persistent disease after chemoradiation results. Patients with pT3/4 disease, lymphovascular space invasion, surgical margins <2 mm may be associated with higher re-recurrence rates and may benefit from more frequent monitoring or treatment escalation.

Effect of high-dose radiation therapy on positive margins after breast-conserving surgery for invasive breast cancer.

Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25Gy for positive margins and 59.31-61.81Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n=55) and 2.4% in the negative margin group (n=495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p=0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p=0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p=0.426). In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.

Different Radiation Dose of Neoadjuvant Chemoradiation for Resectable Thoracic Esophageal Squamous Carcinoma: A Randomized Phase II Clinical Trial

Radiation dose used in the neoadjuvant chemoradiotherapy (nCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) varies in clinical practice, no prospective studies have been conducted on this issue. The hypothesis of this study is that higher radiation dose in nCRT was associated with improved progression free survival in resectable ESCC. A phase II prospective randomized controlled trial was conducted from February 22, 2018 to February 22, 2021 in Zhejiang Cancer Hospital (NCT03381651). Patient with locally resectable advanced thoracic ESCC (cT2-T4aNxM0, T1-3N+M0) were randomized 1:1 to receive nCRT with different radiation doses of 50.4 Gy/28F and 41.4 Gy/23F, weekly TC regimen (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) was administered as concurrent chemotherapy. The primary endpoint was 2-year progression free survival (PFS), and the secondary endpoints included complete pathological response (pCR) rate, overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The last follow-up date was February 22, 2022 and data analysis was performed from May 1, 2022, to October 31, 2022. A total of 147 patients were enrolled in the prospective study, including 72 patients in 50.4 Gy/28F group and 75 patients in 41.4 Gy/23F group. Among all the patients, 101 patients finally underwent surgical resection, 23/46(50%) achieved pCR in the high-dose group, while 18/55(32.7%) achieved pCR in the low-dose group (P = 0.10). In intention-to-treat population analysis, 2-year PFS in the high-dose and low-dose groups were 53.5% (95% CI: 42.9-66.7%) and 45.5% (95% CI: 35.4%-58.5%), respectively, and hazard ratio (HR) was 0.72 (95% CI: 0.46-1.12, P = 0.14). Median PFS were 44.4 months (95% CI: 16-NA) versus 20.8 months (95% CI: 15-NA) in high and low dose groups. 2-year OS in the high and low-dose groups were 61.8% (95% CI: 51.2 -74.5%) and 60.5% (95% CI: 50.3 -72.8%), respectively, with a HR = 0.78(95% CI: 0.48-1.27, P = 0.32). Median OS were not arrived in both groups up to the last follow-up. In addition, 2-year LRFS were 87.9% (95% CI: 78.4-98.5%) and 74.8% (95% CI: 63.3-88.3%) in high and low-dose groups, while 2-year DMFS were 70.6% (95% CI: 58.3-85.5%) and 73.6% (95% CI: 61.7-87.8%), respectively. No significant statistical difference was observed between the two groups in terms of side effects during nCRT and postoperative complications. Our results showed that neoadjuvant high-dose radiotherapy failed to improve overall survival in ESCC. However, it was found that pCR and local tumor control rates tended to be increased at 50.4 Gy/28F, compared to 41.4 Gy/23F, although the trend was not statistically significant. There was no significant difference in treatment side effects between the two groups. Longer-term follow-up is required to verify our findings.

Interim Analysis of a Non-Randomized Prospective Trial Comparing Hypofractionated Post-Mastectomy Radiotherapy (HF-PMRT) to Conventional Post-Mastectomy Radiotherapy (CF-PMRT) for Breast Cancer (BC) Patients

The standard of care for treatment for LABC patients who have undergone modified radical mastectomy (MRM) is PMRT. Post-mastectomy RT (PMRT) for LABC patients has been established in three trials to improve locoregional control and overall survival (OS). A published trial from China showed that HF-PMRT was non-inferior to CF-PMRT. This study was conducted to determine if HF-PMRT can provide similar efficacy and toxicity. A non-randomized prospective trial design was employed to compare HF-PMRT and CF-PMRT in post-MRM BC patients. Patients with pathologically proven BC who underwent MRM without positive margins and with less than 8 positive nodes were included. Informed consent was obtained. Patients decided which treatment they will receive. They received either HF-PMRT of 43.2 Gy in 16 fractions (fx) [2.7 Gy/fx] or CF-PMRT of 50-50.4 Gy in 1.8-2.0 Gy/fx to both chest wall and regional nodes (axillary and supraclavicular) in both regimens. Primary endpoints were 2-year OS and 2-year local recurrence free survival (LRFS). Secondary endpoints include acute and late toxicities. Analysis was done as intention-to treat. An interim analysis of 2-year results is presented. A total of 37 patients were enrolled in two separate cohorts: a single-arm cohort that recruited 10 HF-PMRT patients from 2014-2015 and a two-arm prospective trial that started recruitment last 2019 and included 12 HF-PMRT and 15 CF-PMRT patients. Median follow-up was 35 months. There were more Stage IIB and Stage III for the CF-PMRT arm [p = 0.040]. Treatment interruptions were more frequent in the CF-PMRT arm (100% vs 68%, p = 0.028). The duration of interruption was also longer in CF-PMRT (median 8 vs 3 days) [p < 0.003]. Acute and late toxicities were not statistically different. There was one patient each with RTOG Grade 2 acute skin toxicity in the HF-PMRT (4.55%) and CF-PMRT arms (6.67%) [p = 0.703]. For late toxicities, the HF-PMRT arm had 6 Grade 1 late skin toxicities and 1 Grade 3 late skin toxicity vs 1 Grade 1 late skin toxicity for CF-PMRT arm [p = 0.196]. 2-year OS rate (86.3% vs 100%, p = 0.403) 2-year DFS rate (68.18% and 73.33%, p = 0.126) were both not statistically different. There were no reported locoregional recurrences (LCR). In terms of local control, both arms have showed no LCRs. 2-year OS and DFS rate were no different. As the study has not yet reached the adequate sample size, the non-inferiority of HF-PMRT cannot be definitively concluded. Acute and late toxicities were no different. There was a significantly higher rate of treatment interruptions in the CF-PMRT compared to the HF-PMRT arm. The results of this interim analysis prove to be promising and patients will continue to be accrued. The final results of this study might have tremendous implications in local practice.