The Role of Radiotherapy and Chemoradiation in the Management of Primary Liver Tumours

Due to advances in technical radiotherapy delivery over the past two decades there has been a rapid increase in the use of radiotherapy for intrahepatic malignancies. This overview provides a succinct summary of the current evidence for external beam radiotherapy in the management of primary liver tumours, highlighting areas for future research. Internationally, hepatocellular carcinoma is a leading cause of cancer death and UK incidence rates are rising rapidly. The main risk factor is chronic liver disease and, as a result, most patients will be unsuitable for curative surgical modalities of treatment. Conformal radiotherapy may be used in patients with localised disease who are unsuitable for alternative local therapies. It may also be used in patients with portal venous thrombosis or for palliation in advanced disease. Caution should be used in patients with pre-existent liver dysfunction (Childs Pugh B or C) due to increased rates of toxicity. Stereotactic body radiotherapy has been used for early stage disease, with promising long-term local control rates and a favourable toxicity profile. Stereotactic body radiotherapy has also been investigated as a ‘bridge to transplant’. Charged particle therapy may be used for patients with more advanced liver dysfunction, or as a means of dose escalation, and warrants further investigation in early stage disease. Cholangiocarcinoma is a rare but aggressive primary liver malignancy in which only a minority of patients will be suitable for resection. Conformal radiotherapy and stereotactic body radiotherapy have been used in both the adjuvant and locally advanced settings, although small patient numbers and a lack of prospective trial data limit interpretation of their role. To fully define the role of radiotherapy in the management pathway for primary liver tumours, prospective randomised studies are required.     

保留喉功能下咽癌手术体会

[目的]探讨下咽癌保留喉功能的手术要点。[方法]22例下咽癌患者均行手术治疗,手术方式采用咽部分及垂直半喉切除、下咽＋喉1/4切除、颈侧进路单侧梨状窝切除、颈侧进路下咽局部切除、环后板部分＋披裂切除。切除范围距肿瘤1~2cm,切缘常规送快速冰冻检查。所有病人都行颈淋巴结清扫。部分病人辅以术后放疗。[结果]22例下咽癌病人术后出现轻至中度误咽7例,重度误咽2例。气管套管拔管21例,1例因气道狭窄而留管,拔管率95.5%。所有患者全部恢复发音功能。1例并发咽瘘。死亡率41%,T3、T4死亡6例,T1、T2死亡3例;局部复发4例、颈淋巴转移2例、肝转移1例、肺转移2例;3年生存率77.3%。[结论]下咽癌治疗应以手术为主,放疗为辅。不要为追求彻底而过于扩大正常组织切除范围,因切除过多喉的正常部分并不能改变其预后。对肿瘤基底部的安全切缘要引起我们注意,这是局部肿瘤复发关键。     

The Role of Enhanced Recovery After Surgery for Rectal Cancer

The enhanced recovery after surgery (ERAS) programme is increasingly recognised as the standard of care for patients undergoing colonic cancer surgery, but its applicability to rectal surgery has been questioned. This article analyses the available evidence for the benefit of the individual ERAS elements, with particular reference to rectal surgery. Recent studies have demonstrated the feasibility of ERAS in rectal cancer surgery, and show a reduced length of stay and quicker return of bowel function compared with conventional postoperative care. Ongoing randomised trials will help to clarify the role of ERAS in the era of laparoscopic colonic and rectal cancer surgery.     

Tumor Regression Grade After Neoadjuvant Chemoradiation and Surgery for Low Rectal Cancer Evaluated by Multiple Correspondence Analysis: Ten Years as Minimum Follow-up

Background

The role of Mandard's tumor regression grade (TRG) classification is still controversial in defining the prognostic role of patients who have undergone neoadjuvant chemoradiation (CRT) and total mesorectal excision. The present study evaluated multiple correspondence analysis (MCA) as a tool to better cluster variables, including TRG, for a homogeneous prognosis.

Salvage Surgery After First-Line Alectinib for Locally-Advanced/Metastatic ALK-Rearranged NSCLC: Pathological Response and Perioperative Results

BackgroundThe role of salvage surgery after tyrosine kinase inhibitors in advanced oncogene-addicted non-small cell lung cancer is largely unexplored.PatientsWe aimed to describe the pathological features and surgical early-outcomes of Anaplastic Lymphome Kinase anaplastic lymphome kinase positive non-small cell lung cancer patients undergoing surgery after first-line alectinib treatment. We retrospectively collected and analyzed multicentric data of 10 patients treated with alectinib for advanced-stage anaplastic lymphome kinase positive lung adenocarcinoma who underwent anatomical surgical resection from January 2020 to Decemeber 2021. All patients were treatment naive and received alectinib (600 mg twice daily). Surgery was always proposed after multidisciplinary discussion. The primary endpoints were pathological response and surgical feasibility (technical intraoperative complications, postoperative outcomes).ResultsAlectinib was received for a mean of 212 days before surgery (42-415 days) and was generally interrupted about one week before surgery (range: 0-32 days) with no patient experienced grade 4 toxicity. All patients received an R0 resection with surgery consisting of lobectomy in 8 cases with bilobectomy and (left) pneumonectomy in 1 case each. Intra-operative difficulties were described in 7 cases (70%), mostly due to perivascular fibrosis or thickening of mediastinal lymph nodal tissues. Major and minor complications occurred in 0 and 3 cases (30%), respectively. A pathological complete response and major pathological response (defined as 0% and < 10% viable tumor cells, respectively) were observed in 50% and 90% of cases, respectively. Despite short follow-up, only one tumor recurrence was observed (in the only patient who did not resume alectinib after surgery).InterpretationDespite some technical intraoperative difficulties, salvage surgery was safe and feasible after Alectinib for advanced lung adenocarcinoma.     

Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva

Purpose: To determine the impact of primary or adjuvant chemotherapy and radiation (CRT) on the survival rates of patients with locally advanced vulvar carcinoma.

Methods and Materials: Between 1973 and 1998, 54 patients with vulvar cancer were treated with radiation therapy, among which 20 received CRT, while 34 patients received radiation therapy (RT) alone. Of the 20 patients, 14 were treated for primary or recurrent disease (pCRT), and 6 after radical vulvectomy for high-risk disease (aCRT). Of the 34 patients, 12 were treated primarily (pRT) and 22 received adjuvant treatment (aRT). Chemotherapy consisted of 2 courses of 5-fluorouracil (5-FU) and mitomycin C administered during RT. Six patients received cisplatin in place of mitomycin C. In CRT groups, radiation was administered to the vulva, pelvic, and inguinal lymph nodes to a median dose of 45 Gy with additional 6–17 Gy to gross disease. In RT groups, the median dose to the microscopic diseases was 45 Gy. Nine patients received external beam boost and 16 patients received supplementary brachytherapy in the forms of ²²⁶Ra or ²⁴¹Am plaques to sites of macroscopic disease.

Results: Overall survival was superior in the patients treated with pCRT versus pRT with statistical significance (p = 0.04). There was also a statistically significant improvement in disease-specific (p = 0.03) and relapse-free survival (p = 0.01) favoring pCRT. No statistically significant trends of improved survival rates favoring aCRT over aRT were observed.

Conclusion: Concurrent radiation therapy and chemotherapy decreases local relapse rate, improves disease-specific and overall survival over RT alone as primary treatment for locally advanced vulvar cancer.     

Chemoradiation: A Superior Alternative for the Primary Management of Esophageal Carcinoma

There have been no randomized studies of esophagectomy versus chemoradiation as primary management of esophageal cancer. Review of the literature indicates esophagectomy alone has limited applicability, significant morbidity, higher mortality, and a lesser chance for cure than chemoradiation for patients with squamous cell cancer of the esophagus. The majority of patients with esophageal cancer have disease extending through the esophageal wall or nodal involvement and the prognosis for such patients treated by esophagectomy alone is quite poor, with 5-year survival rate of 10% or less. Recent studies indicate 5-year survival rates with chemoradiation is 20% to 25%. Local failure rates are similar with chemoradiation versus esophagectomy, but swallowing function is superior with chemoradiation. Salvage surgery is possible following chemoradiation for the small percentage of patients who have local-only failure. Chemoradiation is preferred to esophagectomy for patients with squamous cell cancer of the esophagus, and offers significant palliation and the chance for cure for patients with adenocarcinoma of the esophagus as well.     

Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial

Objectives: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. Methods: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). Results: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). Conclusions: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.     

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience

IntroductionAfter failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients.Patients and MethodsThis retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen.ResultsForty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88).ConclusionSecond-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.     

Brachytherapy and Organ Preservation in the Management of Carcinoma of the Prostate

The treatment of organ-confined carcinoma of the prostate with permanent radioisotopes by the retropubic method has generated variable and controversial results. In this article, the technical flaws of the retropubic approach are discussed. Issues of radiobiological factors, dose inhomogeneity, and case selection are addressed relative to the reported results. Recent advances in radioisotope development, computer based dosimetry, and transrectal ultrasound and computed tomographic imaging have fostered techniques of closed transperineal implantation that produce a more homogeneous, reproducible, and larger volume implant with a higher peripheral dose rate than was possible in the past. With a median follow-up of 37 months (range 12 to 78 months), 93% of 291 early stage A-B patients treated with (125)I or (130)Pd alone showed a normal posttreatment prostate-specific antigen (PSA) (median value 0.4). In 160 more advanced stage A-C patients treated with external beam irradiation and implant boost, 85% showed a normal PSA (median value 0.3). The elimination of surgery with these techniques permits outpatient treatment resulting in high patient acceptance. If longer follow-up substantiates the favorable early results, these methods may potentially offer the least morbid and least expensive method of treatment for early stage carcinoma of the prostate.