ABSTRACT
BACKGROUND: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. PATIENTS AND METHODS: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. RESULTS: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3-4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3-77.4) and 85.9% (95% CI: 80.2-90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0-13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5-26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3-5 were significantly associated with worse PFS, OS and metastasis-free survival. CONCLUSIONS: Preoperative IMRT-SIB with the moderate dose intensification of 52.5-57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.
ABSTRACT
BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.
ABSTRACT
Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients.
Subject(s)
COVID-19 , Immunity, Humoral , Humans , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , Vaccination , Antibodies , Immunity, Cellular , Antibodies, ViralABSTRACT
BACKGROUND: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. PATIENTS AND METHODS: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. RESULTS: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). CONCLUSION: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended. CLINICAL TRIALS REGISTRATION NUMBER: CRO-2010-17.
Subject(s)
Capecitabine , Cardiotoxicity , Arrhythmias, Cardiac/epidemiology , Capecitabine/toxicity , Cardiotoxicity/etiology , Exercise , Humans , Incidence , Prospective StudiesABSTRACT
Importance: Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking. Objective: To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes. Design, Setting, and Participants: This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020. Exposures: Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored. Main Outcomes and Measures: The primary outcomes were overall and disease-free survival between the 2 groups. Results: Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P < .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P < .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P < .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P < .001). Conclusions and Relevance: In this cohort study, a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.
Subject(s)
Rectal Neoplasms/surgery , Time-to-Treatment , Aged , Chemoradiotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Italy , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Retrospective StudiesABSTRACT
PURPOSE: To explore the feasibility and efficacy of a dose intensification with Intensity Modulated Radiation Therapy and Simultaneous Integrated Boost (IMRT-SIB) in locally advanced esophageal and gastroesophageal cancer (GEJ). METHODS AND MATERIALS: We retrospectively analyzed a series of 69 patients with esophageal or GEJ cancer treated at our Institute, between 2016 and 2019, with preoperative IMRT and SIB up to 52.5-54 Gy in 25 fractions in 5 weeks and concurrent carboplatin (AUC2) and paclitaxel (50 mg/m2), as in the CROSS regimen. RESULTS: All patients completed the planned IMRT-SIB program with a median of four (range 1-5) cycles of concurrent paclitaxel/carboplatin. Compliance to IMRT-SIB was 93%, whereas 54% of patients received four to five cycles and 87% at least three cycles of concurrent carboplatin/paclitaxel. Grade 3 toxicity was reported in 19% of patients. Complete clinical response (cCR) was achieved in 48%, and 13% had disease progression after chemoradiation (CRT). Overall, 49% of patients underwent surgery; reasons for non-operation included cCR in cervical tumor location (10%) or cCR and patient decision (13%). A pathologic complete response (pCR) was achieved in 44% of resected patients. Postoperative complications and mortality rates were 21 and 6%, respectively. At a median follow-up of 12 months (6-25), 2-year overall and progression-free (PFS) survival rates were 81 and 54%, respectively. No difference in PFS by histologic type in operated patients was reported. Non-operated cCR patients had higher PFS, including cervical locations and selected cCR patients who decided for non-operation (75 vs 30%, p < 0.01). CONCLUSION: The study reported favorable results in safety and feasibility of the IMRT-SIB dose intensification in our preoperative CRT program. The toxicity was acceptable, allowing a high compliance to intensified radiation doses with dose reduction of concurrent paclitaxel/carboplatin in some patients. The high rate of cCR and pCR suggested this intensified program is effective in the preoperative CRT and, for selected responsive patients, in the non-operative approach to esophageal and GEJ cancer. The 2-year survival rates were promising. A prospective study is being planned to confirm these observations.
ABSTRACT
Identifying patients at risk of poor response to neoadjuvant chemoradiotherapy (nCRT) is an emerging clinical need in locally advanced rectal cancer (LARC). SMAD3 is a key player in the chemoradio-resistance phenotype and its expression is both constitutive and locally induced. The aim was to investigate both host (genetic polymorphisms) and tumor SMAD3 profiling to predict response to nCRT. In a group of 76 LARC patients, SMAD3 and phosphorylated-SMAD3 expression was assessed by immunohistochemistry in preoperative tumor tissue. In an expanded study group (n = 378), a set of SMAD3 polymorphisms (rs35874463, rs1065080, rs1061427, rs17228212, rs744910, and rs745103) was analyzed. Association with tumor regression grade (TRG) and patient prognosis (progression-free survival [PFS] and overall survival [OS]) was assessed. Patients with high tumor expression of SMAD3 had a significantly increased risk of poor response (TRG≥2) [cellularity >55% (OR:10.36, p = 0.0004), or moderate/high intensity (OR:5.20, p = 0.0038), or an H-score≥1 (OR:9.84, p = 0.0004)]. Patients carrying the variant SMAD3 rs745103-G allele had a poorer response (OR:0.48, p = 0.0093), a longer OS (HR:0.65, p = 0.0307), and a trend for longer PFS (HR:0.75, p = 0.0944). Patients who carried both high SMAD3 tumor expression and the wild-type rs745103-A allele had an extremely high risk of not achieving a complete response (OR:13.45, p = 0.0005). Host and tumor SMAD3 status might be considered to improve risk stratification of LARC patients to facilitate selection for alternative personalized neoadjuvant strategies including intensified regimens.
ABSTRACT
BACKGROUND: Esophageal cancer (EC) patients presenting a local recurrence following trimodality therapy (chemoradiaton and surgery) have limited palliative treatment options when the three major modalities of therapy have been exhausted. In addition, some patients experience a local recurrence or develop a metachronous cancer in a previously irradiated site, without evidence of systemic disease. For these patients there is a potential for cure, although the risk of further distant recurrences remains high. CASE REPORT: We report of a successful concomitant chemo/SBRT treatment in a case of locally advanced metachronous squamous cervical EC, which was diagnosed in a patient previously treated with trimodality therapy for a squamous tonsillar carcinoma. RESULT: Chemo/SBRT seems to be a reasonable salvage option for patients without distant metastases who have exhausted standard therapies. CONCLUSIONS: Our experience also suggests that a concomitant chemo/SBRT treatment appears to be either feasible or effective and chemo/SBRT can be considered also in selected patients affected by EC with squamous histology and with neoplastic infiltration of the trachea.
Subject(s)
Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Neoplasms, Second Primary/therapy , Radiosurgery , Salvage Therapy/methods , Tonsillar Neoplasms/therapy , Whole-Body Irradiation , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bronchoscopy , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/secondary , Chemotherapy, Adjuvant , Contrast Media , Deglutition Disorders/etiology , Dose Fractionation, Radiation , Esophageal Neoplasms/complications , Esophageal Neoplasms/secondary , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Multimodal Imaging/methods , Neoplasm Staging , Neoplasms, Second Primary/complications , Positron-Emission Tomography , Radiotherapy, Adjuvant , Tomography, X-Ray Computed , Tonsillar Neoplasms/pathology , Treatment Outcome , Weight LossABSTRACT
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by radical surgery including total mesorectal excision (TME) is standard treatment in patients with locally advanced rectal cancer. Emerging data indicate that patients with complete pathologic response (ypCR) after CRT have favorable outcome, suggesting the possibility of less invasive surgical treatment. We analyzed long-term outcome of cT3 rectal cancer treated by neoadjuvant CRT in relation to ypCR and type of surgery. METHODS: The study population comprised 139 patients (93 men, 46 women; median age 62 years) with cT3N0-1M0 mid and distal rectal adenocarcinoma treated by CRT and surgery (110 TME and 29 local excision) at our institution between 1996 and 2008. At pathology, ypCR was defined as no residual cancer cells in the primary tumor. RESULTS: Tumors of 42 patients (30.2%) were classified as ypCR. After a median follow-up of 55.4 months, comparing patients with ypCR to patients with no ypCR, 5-year disease-specific survival was 95.8% versus 78.0% (P = 0.004), and 5-year disease-free survival was 90.1% vs. 64.0% (P = 0.004). In patients with ypCR, no statistically significant outcome difference was observed between TME and local excision. In patients treated by local excision, comparing patients with ypCR to patients with no ypCR, 5-year disease-free survival was 100% vs. 65.5% (P = 0.024), and 5-year local recurrence-free survival was 92.9% vs. 66.7% (P = 0.047). CONCLUSIONS: With retrospective analysis limitations, our data confirm favorable long-term outcome of cT3 rectal cancer with ypCR after CRT and warrant clinical trials exploring local excision surgical strategies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Digestive System Surgical Procedures , Neoadjuvant Therapy , Rectal Neoplasms/mortality , Rectal Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Prognosis , Prospective Studies , Radiotherapy, Adjuvant , Rectal Neoplasms/pathology , Survival RateABSTRACT
PURPOSE: The aim of this study was to evaluate the activity and safety of oxaliplatin/5-fluorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. METHODS: Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m(2)), and leucovorin (20 mg/m(2) on days 1,8,15,29,36,43,50,57) followed by continuous infusion fluorouracil (200 mg/m(2) per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemo-radiotherapy completion. The primary endpoint was 1-year progression-free survival. RESULTS: Forty (68%) patients completed treatment without modifications. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR. At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. CONCLUSIONS: Concurrent oxaliplatin, leucovorin, fluorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Disease-Free Survival , Drug Administration Schedule , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/therapeutic use , Male , Middle Aged , Neoplasm Invasiveness , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Radiation DosageABSTRACT
PURPOSE: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. METHODS AND MATERIALS: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. RESULTS: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). CONCLUSIONS: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.
Subject(s)
Fluorouracil/toxicity , Fluorouracil/therapeutic use , Quinazolines/toxicity , Quinazolines/therapeutic use , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Anal Canal/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/toxicity , Combined Modality Therapy , Diarrhea/chemically induced , Drug Tolerance , Female , Fluorouracil/administration & dosage , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/pathology , Gefitinib , Humans , Infusions, Intravenous , Male , Neoplasm Staging , Quinazolines/administration & dosage , Radiotherapy Dosage , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , SafetyABSTRACT
The aim of the study was to evaluate the feasibility and efficacy of treatment with oxaliplatin, 5-fluorouracil and leucovorin concomitant with radiation therapy in locally advanced oesophageal cancer. Fifty-eight patients with previously untreated, histologically proven oesophageal cancer were enrolled. Downstaged patients underwent either surgery or received brachytherapy. We report the results obtained in the first 54 patients. The median age was 58 years. The diagnosis was squamous cell carcinoma/adenocarcinoma/poorly differentiated: 45/8/1; clinical stage: T3N1M0 38 (70%), T4 10 (19%), M1a 6 (11%). Thirty-nine patients (72%) received the planned 8 weeks of chemotherapy and 45 completed the entire course of scheduled radiotherapy. Four (7%) toxic deaths were recorded, 2 more patients died prematurely from massive oesophageal bleeding and 1 from progression of disease. We recorded 8 (15%) complete responses and 24 (44%) partial responses. Resection was complete (R0) in 24 (80% of resected patients, 44% of treated patients). A complete pathological response was documented in 6 patients (11% of those treated). Postoperative complications were recorded in 8 (25%) patients, with 2 (6.2%) deaths. RO resection was accomplished in 44% of patients. Toxicity was moderate, but postoperative mortality was not negligible. Survival data are awaited before a phase III comparison with cisplatin-containing chemo-radiotherapy may be considered.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Neoadjuvant Therapy , Adult , Aged , Carcinoma/surgery , Esophageal Neoplasms/surgery , Feasibility Studies , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Treatment OutcomeSubject(s)
Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Radiotherapy, Computer-Assisted , Chemotherapy, Adjuvant/methods , Cisplatin/therapeutic use , Clinical Trials as Topic , Combined Modality Therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Pancreatic Neoplasms/etiology , Pancreatic Neoplasms/mortality , Radiotherapy, Adjuvant/methods , Radiotherapy, Computer-Assisted/methods , Survival Rate , GemcitabineABSTRACT
During the past two decades, significant advances have been made in the management of patients with rectal cancer. A number of clinical studies have demonstrated the efficacy of preoperative chemoradiation therapy with 5-fluorouracil (5-FU)-based regimens in decreasing local recurrences and improving survival and the likelihood of sphincter preservation. Although 5-FU has been the standard drug used in combination with radiation therapy for many years, new effective drugs including capecitabine, raltitrexed, irinotecan and oxaliplatin have been recently investigated in combination with radiation therapy in the preoperative setting. In addition, novel targeted biological agents including epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors have been shown to enhance the antitumor effect of both radiation and chemotherapy and are currently being explored in initial clinical trials. In the present review we summarize the results of adjuvant therapy. In addition, we will discuss the recently reported phase I-II trials with new drug plus radiation combinations in the preoperative treatment of patients with rectal cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Chemotherapy, Adjuvant , Clinical Trials as Topic , Humans , Neoadjuvant Therapy/methods , Radiotherapy, Adjuvant , Rectal Neoplasms/surgeryABSTRACT
The positive results recently reported by the Intergroup 0116 Study with adjuvant chemoradiation have stimulated an increasing interest in the combined modality treatment of gastric cancer. The significant improvement in disease-free and overall survival reported in this study was related mainly to an improvement in local control rather than to a decrease in the incidence of metastatic disease. Therefore, new and potentially more effective chemotherapy regimens could be considered and the feasibility of their integration with radiation therapy needs to be explored to further improve the treatment in gastric cancer. Our experience with combined radiation therapy and 5-FU-with or without 5-FU based chemotherapy--in unresectable and in partially or radically resected gastric cancer is retrospectively reviewed. In addition, an initial prospective evaluation of the feasibility and toxicity of radiation and 5-FU following adjuvant chemotherapy with modern platinum containing regimens is reported. Our data and the current available experiences with investigational approaches in gastric cancer involving preoperative chemotherapy and intraoperative radiotherapy will be considered in exploring a new combined modality treatment program.