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JAMA Oncology Sep 2022National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial.
IMPORTANCE
National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear.
OBJECTIVE
To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021.
INTERVENTIONS
Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours).
MAIN OUTCOMES AND MEASURES
Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection.
RESULTS
Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02839343.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Pancreas; Pancreatic Neoplasms; Prospective Studies
PubMed: 35834226
DOI: 10.1001/jamaoncol.2022.2319 -
International Journal of Radiation... May 2021Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated... (Review)
Review
PURPOSE
Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.
METHODS AND MATERIALS
Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).
RESULTS
Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.
CONCLUSIONS
Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.
Topics: Adenoma; Blindness; Cavernous Sinus; Craniopharyngioma; Humans; Maximum Tolerated Dose; Meningeal Neoplasms; Meningioma; Models, Biological; Models, Theoretical; Optic Chiasm; Optic Nerve; Organs at Risk; Pituitary Neoplasms; Radiation Dose Hypofractionation; Radiation Tolerance; Radiosurgery; Radiotherapy Dosage; Re-Irradiation; Skull Base Neoplasms; Visual Acuity; Visual Fields
PubMed: 29534899
DOI: 10.1016/j.ijrobp.2018.01.053 -
The Lancet. Gastroenterology &... Feb 2023Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The... (Randomized Controlled Trial)
Randomized Controlled Trial
Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial.
BACKGROUND
Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery.
METHODS
ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m on days 1, 8, and 15, and oral capecitabine 830 mg/m twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m, irinotecan 180 mg/m, folinic acid given according to local practice, and fluorouracil 400 mg/m bolus injection on days 1 and 15 followed by 2400 mg/m 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete.
FINDINGS
Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia.
INTERPRETATION
Recruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma.
FUNDING
Cancer Research UK.
Topics: Humans; Irinotecan; Neoadjuvant Therapy; Pancreatic Neoplasms; Capecitabine; Oxaliplatin; Antineoplastic Combined Chemotherapy Protocols; Gemcitabine; Leucovorin; Neoplasm Recurrence, Local; Fluorouracil; Chemoradiotherapy; Carcinoma, Pancreatic Ductal
PubMed: 36521500
DOI: 10.1016/S2468-1253(22)00348-X -
The Lancet. Oncology Aug 2015Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery...
BACKGROUND
Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response.
METHODS
We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816.
FINDINGS
Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients).
INTERPRETATION
Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.
FUNDING
National Institutes of Health National Cancer Institute.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Canada; Chemoradiotherapy, Adjuvant; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Intention to Treat Analysis; Leucovorin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Odds Ratio; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Remission Induction; Time Factors; Treatment Outcome; United States
PubMed: 26187751
DOI: 10.1016/S1470-2045(15)00004-2 -
Annals of Oncology : Official Journal... Aug 2019This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical... (Comparative Study)
Comparative Study Randomized Controlled Trial
Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.
BACKGROUND
This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications.
PATIENTS AND METHODS
Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin).
RESULTS
Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively.
CONCLUSION
The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated.
CLINICAL TRIAL NUMBER
The trial is registered as ClinicalTrials.gov number NCT00833131.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Consolidation Chemotherapy; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Poland; Proctectomy; Rectal Neoplasms; Rectum; Time Factors; Young Adult
PubMed: 31192355
DOI: 10.1093/annonc/mdz186 -
Annals of Oncology : Official Journal... May 2016Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.
BACKGROUND
Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules.
PATIENTS AND METHODS
Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups.
RESULTS
Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54.
CONCLUSIONS
No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy.
CLINICAL TRIAL NUMBER
The trial is registered as ClinicalTrials.gov number NCT00833131.
Topics: Aged; Chemoradiotherapy; Combined Modality Therapy; Consolidation Chemotherapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms
PubMed: 26884592
DOI: 10.1093/annonc/mdw062 -
International Journal of Bioprinting 2021Bolus is a kind of auxiliary device used in radiotherapy for the treatment of superficial lesions such as skin cancer. It is commonly used to increase skin dose and... (Review)
Review
Bolus is a kind of auxiliary device used in radiotherapy for the treatment of superficial lesions such as skin cancer. It is commonly used to increase skin dose and overcome the skin-sparing effect. Despite the availability of various commercial boluses, there is currently no bolus that can form full contact with irregular surface of patients' skin, and incomplete contact would result in air gaps. The resulting air gaps can reduce the surface radiation dose, leading to a discrepancy between the delivered dose and planned dose. To avoid this limitation, the customized bolus processed by three-dimensional (3D) printing holds tremendous potential for making radiotherapy more efficient than ever before. This review mainly summarized the recent development of polymers used for processing bolus, 3D printing technologies suitable for polymers, and customization of 3D printing bolus. An ideal material for customizing bolus should not only have the feature of 3D printability for customization, but also possess radiotherapy adjuvant performance as well as other multiple compound properties, including tissue equivalence, biocompatibility, antibacterial activity, and antiphlogosis.
PubMed: 34805595
DOI: 10.18063/ijb.v7i4.414 -
The Lancet. Oncology Sep 2017Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal... (Comparative Study)
Comparative Study Randomized Controlled Trial
First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials.
BACKGROUND
Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.
METHODS
FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m bolus fluorouracil followed by a 2400 mg/m continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m bolus fluorouracil followed by a 2400 mg/m continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).
FINDINGS
Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6-58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90-1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0-24·5) compared with 23·3 months (21·8-24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3-4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group.
INTERPRETATION
Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed.
FUNDING
Bobby Moore Fund of Cancer Research UK, Sirtex Medical.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Female; Humans; Liver Neoplasms; Male; Middle Aged; Radiotherapy, Adjuvant; Treatment Outcome
PubMed: 28781171
DOI: 10.1016/S1470-2045(17)30457-6 -
Journal of Radiation Research May 2022The commercial flat bolus cannot form perfect contact with the irregular surface of the patient's skin, resulting in an air gap. The purpose of this study was to...
The commercial flat bolus cannot form perfect contact with the irregular surface of the patient's skin, resulting in an air gap. The purpose of this study was to evaluate the feasibility of using a 3D customized bolus from silicone rubber. The silicone rubber boluses were studied in basic characteristics. The 3D customized bolus was fabricated at the nose, cheek and neck regions. The point dose and planar dose differences were evaluated by comparing with virtual bolus. The hardness, thickness, density, Hounsfield unit (HU) and dose attenuation of the customized bolus were quite similar to a commercial bolus. When a 3D customized bolus was placed on the RANDO phantom, it can significantly increase buildup region doses and perfectly fit against the irregular surface shape. The average point dose differences of 3D customized bolus were -1.1%, while the commercial bolus plans showed -1.7%. The average gamma results for planar dose differences comparison of 3D customized bolus were 93.9%, while the commercial bolus plans were reduced to 91.9%. Overall, A silicone rubber bolus produced the feasible dosimetric properties and could save cost compared to a commercial bolus. The 3D printed customized bolus is a good buildup material and could potentially replace and improve treatment efficiency.
Topics: Humans; Phantoms, Imaging; Printing, Three-Dimensional; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Silicone Elastomers
PubMed: 35420693
DOI: 10.1093/jrr/rrac013 -
Reports of Practical Oncology and... 2022Approximately 50% of melanomas, 30-40% of lung and breast cancers and 10-20% of renal and gastrointestinal tumors metastasize to the adrenal gland. Metastatic adrenal... (Review)
Review
Approximately 50% of melanomas, 30-40% of lung and breast cancers and 10-20% of renal and gastrointestinal tumors metastasize to the adrenal gland. Metastatic adrenal involvement is diagnosed by computed tomography (CT ) with contrast medium, ultrasound (which does not explore the left adrenal gland well), magnetic resonance imaging (MRI) with contrast medium and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDGPET-CT ) which also evaluates lesion uptake. The simulation CT should be performed with contrast medium; an oral bolus of contrast medium is useful, given adrenal gland proximity to the duodenum. The simulation CT may be merged with PET-CT images with FDG in order to evaluate uptaking areas. In contouring, the radiologically visible and/or uptaking lesion provides the gross tumor volume (GTV ). Appropriate techniques are needed to overcome target motion. Single fraction stereotactic radiotherapy (SRT ) with median doses of 16-23 Gy is rarely used. More common are doses of 25-48 Gy in 3-10 fractions although 3 or 5 fractions are preferred. Local control at 1 and 2 years ranges from 44 to 100% and from 27 to 100%, respectively. The local control rate is as high as 90%, remaining stable during follow-up when BED is equal to or greater than 100 Gy. SRT-related toxicity is mild, consisting mainly of gastrointestinal disorders, local pain and fatigue. Adrenal insufficiency is rare.
PubMed: 35402020
DOI: 10.5603/RPOR.a2021.0104