Adjuvant Pelvic Radiotherapy vs.Sequential Chemoradiotherapy for High-Risk StageⅠ-ⅡEndometrial Carcinoma

Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival （OAS）, and progression free survival （PFS）; to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-1I endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone （arm Ⅰ）（57 patients） or with sequential carboplatin （AUCS-6） and paclitaxel （135-175 mg/m^2） with radiotherapy （arm Ⅱ） （51 patients）. Radiotherapy was performed through the four-field box technique at doses of 45-50 Gy （1.8 Gy/day × 5 days/week）. Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm Ⅰ and arm Ⅱ, respectively, without febrile neutropenia. All patients experienced hair loss. Chernoradiotherapy arm was associated with a lower incidence rate of relapse （9.8% vs. 22.7%）. After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy （P=0.02 and 0.03, respectively）. In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage Ⅰ-Ⅱ endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage Ⅰ-Ⅱ endometrial carcinoma.

Refining the American Urological Association and American Society for Radiation Oncology guideline for adjuvant radiotherapy after radical prostatectomy using the pathologic Gleason score

Recently, it has been suggested that the guideline for adjuvant radiotherapy （ART） following radical prostatectomy （RP） sponsored by the American Urological Association and American Society for Radiation Oncology （AUA/ASTRO） may result in a significant overtreatment. Thus, the objective of the present study was to refine the AUA/ASTRO guideline for ART in patients at risk for biochemical recurrence （BCR） after RP. To this end, we reviewed our prospectively maintained database and selected 193 patients who met the AUA/ASTRO ART criteria. With a median follow-up of 24.0 months, BCR rate was 17.6% （34/193）. When stratified by the Gleason score, BCR rate in men with Gleason score 6 was 6.8%. There was no significant association between BCR-free survival and surgical margin （P= 0.690） and pathologic stage （P= 0.353） in patients with the Gleason score 6. However, in patients with positive surgical margins （PSMs）/pathologic stage ≥T3, there was a significant difference in BCR-free survival according to Gleason score （≤7 vs8-10, P= 0.047）. Multivariate Cox regression analysis demonstrated that pathologic stage ≥T3 （HR = 2.106; P = 0.018）, PSMs （HR = 2.411; P = 0.003）, and pathologic Gleason score 8-10 （HR = 4.715; P 〈 0.001） were independent predictors of BCR after RP. Therefore, in addition to pathologic stage 〉T3 and PSMs, Gleason score 8-10 predicts 8CR after RP. In patients with Gleason score 6, observation rather than ART may be more appropriate regardless of stage and surgical margin status.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma:comparison of long-term outcome between radiotherapy and chemotherapy

AIM:To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma(NRSTS),and to compare the treatment outcome between postoperative radiotherapy(RT) and chemotherapy in a retrospective analysis nearly 20y.METHODS:A retrospective cohort study of 56 patients with orbital NRSTS were reviewed,34 of whom received postoperative RT,and 22 received postoperative chemotherapy.The clinicopathological features,local recurrence,metastases,and survival data were recorded.Survival analysis was performed using the Kaplan-Meier method.RESULTS:During follow-up(111.8mo,ranged 8-233mo) for 56 patients,19 patients of them developed local recurrence,and 7 patients developed distant metastases.Fifteen patients died during follow-up period.Overall survival rates considering the whole study group was 78.57% at 5y,and 72.16% at 10y after the initial diagnosis.Compared with chemotherapy,RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy,0.263,95% confidence interval(CI),0.095-0.728,P=0.0015];with lower risk of distant metastasis(hazard ratio for RT vs chemotherapy,0.073,95%CI,0.015-0.364,P=0.0014);and with lower risk of death from disease(hazard ratio for RT vs chemotherapy,0.066,95%CI,0.022-0.200,P<0.0001).The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group.CONCLUSION:In patients with orbital NRSTS,postoperative RT provides better control of local recurrence,distant metastasis,and death from disease than chemotherapy.RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Impact of timing of adjuvant radiotherapy on locoregional control in patients with high-risk endometrial cancer

Aim:High-risk endometrial cancer has a higher risk of regional and distant recurrence.We sought to examine our institutional experience regarding the timing of adjuvant radiotherapy and local failure(LF),locoregional failure(LRF),distant failure(DF),and overall survival(OS).Methods:We retrospectively reviewed a database of patients with high-risk endometrial cancer treated with sequential chemotherapy followed by adjuvant external beam radiation therapy(EBRT)with or without brachytherapy from 2012 to 2019.Results:One hundred thirty-one patients were identified.The median age at diagnosis was 65(range 32-81).The most prevalent FIGO stages were IIIB(28.2%,n=37),IIIC1(19.8%,n=26),and IIIA(17.6%,n=23).Of the patients,29%(n=38)had positive lymph nodes and 71%(n=93)had negative lymph nodes.The most prevalent histology was endometrioid(71%,n=93),serous(12.2%,n=16),clear cell(9.2%,n=12),and other(7.6%,n=10).Moreover,100%(n=131)of the patients completed EBRT.The mean EBRT dose was 49.6 Gy(range 45-50.4).The median number of days between surgery and EBRT was 212.4 days(range 103-219).The mean brachytherapy dose was 14.7 Gy(range 12-30).The cumulative incidence of LF was 6.1%,LRF was 19%,DF was 19%,and the median survival was 33.4 months.For patients who completed EBRT 180 days after surgery,LRF(HR 3.55[1.23-10.2],P=0.013),LF(HR 1.91[0.4-8.9],P=0.429),DF(HR 0.91[0.41-2],P=0.806),and OS(HR 0.92[0.33-2.6],P=0.87).Conclusion:In our cohort of patients with high-risk endometrial cancer treated with chemotherapy followed by radiotherapy,delaying RT was associated with an increased risk of LRF but no differences in DF or OS.

Benefit of adjuvant chemoradiotherapy in patients with pathologically lymph node-positive and locally advanced gastric cancer

Objective This study aimed to compare the effectiveness of adjuvant chemoradiotherapy(CRT)and adjuvant chemotherapy(ChT)for T3–4/N+gastric cancer(GC)following D2/R0 dissection,and identify the specific subgroups that could benefit from adjuvant CRT.Methods All eligible patients were divided into the CRT group and ChT group.We assessed the survival outcomes and patterns of recurrence for each group,and determined the prognostic factors for survival by performing Cox proportional risk regression analyses.Results A total of 192 gastric cancer patients were included in the study.The estimated 3-year and 5-year disease-free survival(DFS)probabilities in the CRT and ChT groups were 52.9%vs.36.7%(P=0.024)and 41.2%vs.31.1%(P=0.148),respectively,and the estimated 3-year and 5-year overall survival(OS)probabilities were 82.4%vs.70.0%(P=0.044)and 52.0%vs.35.6%(P=0.022).Patients in the CRT group had a lower risk of locoregional recurrence than those in the ChT group(20.6%vs.34.4%;P=0.031).The subset analyses revealed that patients with stage N1–2 disease were more likely to benefit from adjuvant CRT than from adjuvant ChT(DFS:53.1%vs.36.4%;P=0.039;OS:53.1%vs.38.6%;P=0.036).Conclusion For locally advanced gastric cancer patients with LN+,adjuvant CRT showed superior survival benefits compared with adjuvant ChT alone.Patients with N1–2 achieved better survival from adjuvant CRT.

Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage Ⅱ and Ⅲ rectal adenocarcinoma:The Freiburg experience(1989-2002)

AIM： To evaluate the long-term outcome of standard 5-FU based adjuvant or neoadjuvant radiochemotherapy and to identify the predictive factors, especially anemia before and after radiotherapy as well as hemoglobin increase or decrease during radiotherapy. METHODS： Two hundred and eighty-six patients with Union International Contre Cancer （UICC） stage Ⅱ and Ⅲ rectal adenocarcinomas, who underwent resection by conventional surgical techniques （low anterior or abdominoperineal resection）, received either postoperative （n = 233） or preoperative （n = 53） radiochemotherapy from January 1989 until July 2002. Overall survival （OAS）, cancer-specific survival （CSS）, disease-free survival （DFS）, local-relapse-free （LRS） and distant-relapse-free survival （DRS） were evaluated using Kaplan-Meier, Log-rank test and Cox＇s proportional hazards as statistical methods. Multivariate analysis was used to identify prognostic factors. Median follow-up time was 8 years. RESULTS： Anemia before radiochemotherapy was an independent prognostic factor for improved DFS （risk ratio 0.76, P= 0.04） as well as stage, grading, R status （free radial margins）, type of surgery, carcinoembryonic antigen （CEA） levels, and gender. The univariate analysis revealed that anemia was associated with impaired LRS（better local control） but with improved DFS. In contrast, hemoglobin decrease during radiotherapy was an independent risk factor for DFS （risk ratio 1.97, P= 0.04）. During radiotherapy, only 30.8% of R0-resected patients suffered from hemoglobin decrease compared to 55.6% if R1/2 resection was performed （P= 0.04）. The 5-year OAS, CSS, DFS, LRS and DRS were 47.0%, 60.0%, 41.4%, 67.2%, and 84.3%, respectively. Significant differences between preoperative and postoperative radiochemotherapy were not found. CONCLUSION ： Anemia before radiochemotherapy and hemoglobin decrease during radiotherapy have no predictive value for the outcome of rectal cancer. Stage, grading, R status （free radial margins）, type of surgery, CEA levels, and gender have predictive value for the outcome of rectal cancer.

Adjuvant therapy for gastric cancer:What have we learned since INT0116?

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapsefree and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

A study evaluating the impact of nerve preserving surgery and adjuvant pelvic irradiation for rectal cancer on quality of life

Objective： Preservation of the pelvic autonomic nerves in order to lower bladder and sexual dysfunction after radical rectal cancer surgery ＆ to evaluate functional outcome, local recurrence. Methods： A prospective study was under- taken on Egyptian patients. Forty one patients participated in the study in the period from December 2002 till June 2004 where they underwent radical surgery but with preservation of the pelvic autonomic nerves this was followed by adjuvant pelvic radiotherapy. Results： Six months, 1-year and 2-year follow-up of urinary function was complete in 32 out of 41 （78%）, 30 out of 41 （73%） and 27 out of 41 patients （65%） respectively There was no statistically significant correlation between the extent of nerve preservation and the reported minor voiding dysfunction. None of the patients reported major incontinence. Six months, 1-year and 2-year follow-up of sexual function revealed that 22 out of 41 patients （53%） were sexually active. Three out of 41 patients （7.3%） developed local recurrence. 38 （92.7%） patients were free of local recurrence, regarding pa- tients who received adjuvant radiotherapy 3 out of the 34 （8.8%） patients developed local pelvic recurrence while 9 patients （26.5%） developed distant metastases （3 of them did not receive adjuvant chemotherapy）, while patients who received adju- vant chemotherapy, 2 out of 20 patients （10%） developed local recurrence while distant metastases developed in 6 patients （30%）. Conclusion： Preservation of the pelvic autonomic nerves minimizes bladder and sexual dysfunction especially in male patients after rectal cancer surgery.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background： We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma（PAC）.Methods： A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.Results： Of 563 patients, 472 received adjuvant chemotherapy（CT） alone, chemoradiotherapy（CRT） alone, and chemoradiotherapy plus chemotherapy（CRT-CT） were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival（RFS） and overall survival（OS） were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant differencebetween groups when patients with node-negative disease or patients with or without positive surgical margins were considered.Conclusions： Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy

AIM: To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. METHODS: Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resect-able locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. RESULTS: The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). CONCLUSION: MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.

Current concepts in the surgical treatment of skeletal metastases

Symptomatic metastatic bone disease affects a large proportion of patients with malignant tumours and significantly impairs patients’quality of life.There are still controversies regarding both surgical indications and methods,mainly because of the relatively few high-quality studies in this field.Generally,prosthetic reconstruction has been shown to result in fewer implant failures and should be preferred in patients with a good prognosis.Survival estimation tools should be used as part of preoperative planning.Adjuvant treatment,which relies on radiotherapy and inhibition of osteoclast function may also offer symptomatic relief and prevent implant failure.In this review we discuss the epidemiology,indications for surgery,preoperative planning,surgical techniques and adjuvant treatment of metastatic bone disease.

Role of adjuvant(chemo)radiotherapy for resected extrahepatic cholangiocarcinoma:a meta-analysis

Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .

Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.

The role of radiation for pancreatic adenocarcinoma

Pancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent resection.Improvements in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment strategies.The role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability,and the use of antiquated radiation delivery techniques and chemotherapy regimens.Current level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma(PDAC)are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront surgery.In the adjuvant setting,data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional recurrence.Here we review existing data regarding the role of radiation in PDAC.

Clinical improvement in the therapy of aural keloids

Background Keloids have a predilection for the aural region because of the special shape of the pinna. It is difficult to resect keloids entirely and maintain a satisfactory pinnal shape. Surgical excision in combination with radiotherapy is considered to be the most efficacious treatment available for severe keloids. This study was conducted to evaluate the treatment of aural keloids with intralesional excision and immediate postoperative adjuvant radiotherapy. Methods Forty-six patients with a combined total of 74 aural keloids were treated by intralesional excision and immediate postoperative adjuvant radiotherapy. All patients received a total dose of 20 Gy in 10 consecutive days. The time interval between keloid excision and delivery of the first radiotherapy fraction was 〈24 hours in all cases. The median follow-up was 2.2 years. Results Twenty-nine patients with 48 keloids （64.9%） were highly satisfied with their outcome, and were rated as good by the surgeon. Six patients with 12 keloids （16.2%） showed general satisfaction but wanted aesthetic refinement, and these patients were rated as fair by the surgeon. Three patients with four keloids （5.4%） showed no evidence of recurrence after surgery, but disliked the result because of the discoloration and irregularity of the scar surface. These patients were rated as poor by the surgeon. Partial recurrence occurred in 8 patients with 10 keloids （13.5%）. No major complications were observed. Conclusion Intralesional excision and immediate postoperative adjuvant radiotherapy is well tolerated and very effective in Dreventing recurrence of aural region keloids.