High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective.

BACKGROUND: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported. METHODS: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV. RESULTS: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients. CONCLUSIONS: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

BACKGROUND: Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. METHODS: This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). RESULTS: Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5 months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). CONCLUSION: In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Anal squamous cell carcinoma: Impact of radiochemotherapy evolution over years and an explorative analysis of MRI prediction of tumor response in a mono-institutional series of 131 patients.

Introduction: Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure. Patients and methods: Between 2010 and 2020, ASCC stages I-III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS® v.26.0 software (IBM®). Results: A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix's Large Area High Gray Level Emphasis (GLSZM's LAHGLE), and GTV volume. Conclusions: Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM's LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials.

Stereotactic prostate radiotherapy with or without androgen deprivation therapy, study protocol for a phase III, multi-institutional randomized-controlled trial.

Objective: The therapeutic landscape for localized prostate cancer (PC) is evolving. Stereotactic radiotherapy (SRT) has been reported to be at least not inferior to standard radiotherapy, but the effect of androgen deprivation therapy (ADT) in this setting is still unknown and its use is left to clinical judgment. There is therefore the need to clarify the role of ADT in association with SRT, which is the aim of the present study. Methods: We present a study protocol for a randomized, multi-institutional, Phase III clinical trial, designed to study SRT in unfavorable intermediate and a subclass of high-risk localized PC. Patients (pts) will be randomized 1:1 to SRT + ADT or SRT alone. SRT will consists in 36.25 Gy in 5 fractions, ADT will be a single administration of Triptorelin 22.5 mg concurrent to SRT. Primary end point will be biochemical disease-free survival. Secondary end points will be disease-free survival, freedom from local recurrence, freedom from regional recurrence, freedom from distant metastasis and overall survival (OS); quality of life QoL and patient reported outcomes will be an exploratory end point and will be scored with EPIC-26, EORTC PR 25, IPSS, IIEF questionnaires in SRT + ADT and SRT alone arms. Moreover, clinician reported acute and late toxicity, assessed with CTCAE v. 5.0 scales will be safety end points. Results: Sample size is estimated of 310 pts. For acute toxicity and quality of life results are awaited after 6 months since last patient in, whereas, for efficacy end points and late toxicity mature results will be available 3-5 years after last patient in. Conclusion: Evidence is insufficient to guide decision making concerning ADT administration in the new scenario of prostate ultra-hypofractionation. Hence, the need to investigate the ADT role in SRT specific setting. Advances in knowledge: The stereotactic prostate radiotherapy with or without ADT trial (SPA Trial) has been designed to establish a new standard of care for SRT in localized unfavorable intermediate and a subclass of localized high risk PC.

Two months of radiation oncology in the heart of Italian "red zone" during COVID-19 pandemic: paving a safe path over thin ice.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy "red-zone". METHODS: Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed. RESULTS: Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff. CONCLUSIONS: Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.

Can brachytherapy be properly considered in the clinical practice? Trilogy project: The vision of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) Interventional Radiotherapy study group.

PURPOSE: Brachytherapy (BT, interventional radiotherapy - IRT) is a kind of radiation therapy, in which the radioactive source is placed nearby or even inside the cancer itself. Even though this kind of radiation therapy appears effective and valuable, BT has been facing a slow but progressive decline over the past decades in Europe, particularly in Italy. Aims of this study were to identify the practical and theoretical reasons why BT is facing a slow decline in Italy, and to define a vision of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and a strategy about this emerged issues. MATERIAL AND METHODS: A programmatic path divided into three steps like a trilogy was launched by AIRO Interventional Radiotherapy study group. The study group performed an initial data collection to highlight both the clinical and the educational topics and problems through specific surveys. After having analyzed the results of the surveys and shared a vision about the emerged issues, a specific strategy was adopted. RESULTS: Four relevant domains were identified and for each ones, a strategy has been discussed and defined. This manuscript shows in detail the individual actions defined (accomplished or in progress). CONCLUSIONS: The AIRO vision implies that specific strategic interventions must be carried out in the field of national guidelines, education, research, and communication with patients and colleagues of other specialties in an interdisciplinary setting.

The role of palliative interventional radiotherapy (brachytherapy) in esophageal cancer: An AIRO (Italian Association of Radiotherapy and Clinical Oncology) systematic review focused on dysphagia-free survival.

PURPOSE: The aim of this review was to examine efficacy of palliative interventional radiotherapy (IRT) in esophageal cancer compared with other treatment in terms of dysphagia-free survival (DyFS) and safety. METHODS AND MATERIAL: A systematic research using PubMed, Scopus, and Cochrane library was performed to identify full articles evaluating the efficacy of IRT as palliation in patients with esophageal cancer. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical study as full text of patients with symptomatic esophageal cancer treated with IRT alone or in combination with other treatment. Conference paper, survey, letter, editorial, book chapter, and review were excluded. Time restriction (1990-2018) as concerns the years of the publication was considered. The primary outcome was the duration of dysphagia relief (DyFS) after brachytherapy vs. other treatment (external-beam radiotherapy, photodynamic therapy, argon plasma coagulation, stent, and laser) during followup. Secondary outcomes included overall survival and adverse event rates. RESULTS: The literature search resulted in 554 articles. Sixty-six articles were assessed via full text for eligibility. Of these, 59 articles were excluded for various reasons, leaving seven randomized studies. The number of evaluated patients was 905 patients, and median age was 70.5 years. In the IRT group, the median DyFS was 99 days, the most relevant G3-G4 toxicity were fistula development and stenosis reported, respectively, in 8.3% and 12.2%; the overall median survival was 175.5 days. CONCLUSION: In conclusion, we provided evidence-based support that IRT is an effective and safe treatment option; therefore, its underuse is no longer justified.

Current state of interventional radiotherapy (brachytherapy) education in Italy: results of the INTERACTS survey.

PURPOSE: Increased complexity of interventional radiotherapy (brachytherapy - BT) treatment planning and quality control procedures has led to the need of a specific training. However, the details of the features of BT learning objectives and their distribution in the training paths of the Italian Radiation Oncology Schools are not known. This paper aims to provide the actual 'state-of-the-art' of BT education in Italy and to stimulate the debate on this issue. MATERIAL AND METHODS: All the Italian radiation oncology schools' directors (SD) were involved in a web survey, which included questions on the teaching of BT, considering also the 2011 ESTRO core curriculum criteria. The survey preliminary results were discussed at the 8th Rome INTER-MEETING (INTERventional Radiotherapy Multidisciplinary Meeting), June 24th, 2017. The present paper describes the final results of the survey and possible future teaching strategies resulting from the discussion. RESULTS: A total of 23 SDs answered the survey. The results evidenced a wide heterogeneity in the learning activities available to trainees in BT across the country. While theoretical knowledge is adequately and homogeneously transmitted to trainees, the types of practice to which they are exposed varies significantly among different schools. CONCLUSIONS: This survey proves the need for an improvement of practical BT education in Italy and the advisability of a national BT education programme networking schools of different Universities. Beside the organization of national/international courses for BT practical teaching, Universities may also establish post-specialization courses ('second level' Masters) to allow professionals (already certified in radiation oncology) to acquire more advanced BT knowledge.

HAPPY - Humanity Assurance Protocol in interventional radiotheraPY (brachytherapy) - an AIRO Interventional Radiotherapy Study Group project.

PURPOSE: Interventional procedures may produce emotional distress, particularly in interventional radiotherapy (IRT, brachytherapy - BT). This work would like to propose a series of recommendations/interventions to guarantee a human approach in order to favor the psychological well-being of the patient during interventional radiotherapy. MATERIAL AND METHODS: Thirty patients affected by gynecological cancer and treated with endovaginal high-dose-rate IRT (HDR-IRT) were selected from January to March 2019. A specific Multiprofessional Task Group (MTG) was defined in order to analyze the needs of patients. Each component of the task group spoke with the patients to examine their needs and to investigate their fears and perception. The results of the MTG were subjected to evaluation by an Expert Team (ET) of 4 physicians from 4 different institutions for a final evaluation. Both teams discussed the patient's needs to generate a list of necessary interventions to fulfill every single need in order to obtain their inner well-being. Another team (Master Team - MT) performed an independent check. RESULTS: All patients suggest that the main issue is the "lack of information and fear of the unknown". The fear of feeling pain was a significant source of concern, sadness, and vulnerability for the majority of the patients (76.6%). All patients do not appreciate the use of the word "bunker" to describe the treatment place. In 33.3% of patients the word "brachytherapy" (often unknown) determines insecurity while the term "interventional radiotherapy" reassures. Ninety percent of patients preferred to perform the external genital depilation at home and 80% of them would like the bladder catheter to be placed immediately before the procedure. MTG and ET defined nine "HAPPY recommendations". The MT approved the protocol without changes. CONCLUSIONS: The aim of the present paper was to produce a protocol consisting in intervention that could improve the internal serendipity and emotional state of patients who underwent HDR-IRT.

Postoperative radiotherapy for prostate cancer: the sooner the better and potential to reduce toxicity even further.

PURPOSE: To evaluate biochemical relapse-free survival (bRFS), overall survival (OS), late rectal and bladder toxicities in a retrospective single institution series, also applying an in-house software for biological dose calculation. METHODS: 258 patients submitted to radiotherapy after prostatectomy were considered. Differences between groups were calculated using the log-rank test and the relevant clinical and therapeutic variables were considered for multivariate analysis. PRODVH is an in-house system able to calculate mean dose-volume histograms (DVHs) of a series of patients, to convert them in biologically effective DVHs (BEDVHs) and allowing to compare them with ANOVA and t Student test. RESULTS: Adjuvant radiotherapy (ART) and salvage radiotherapy (SRT) were performed in 131 (50.8%) and 127 patients (49.2%). At multivariate analysis advanced T stage, androgen deprivation total (ADT) and SRT resulted as independent variables related to a worst bRFS (p = 0.019, 0.001 and 0.02), while GS > 7 and SRT affected negatively OS (p 0.047 and 0.039). High grade toxicity events occurred mainly in patients treated with 3-dimensional conformal radiotherapy (3DCRT) (proctitis p = 0.006; cystitis: p = 0.041). A significantly more favorable mean rectum BEDVH for patients with G0 or G1 rectal toxicity was shown (p < 0.001). Mean BEDVH for both bladder (p < 0.01) and rectum (p < 0.05) were also significantly better for volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) plans than for 3DCRT plans. CONCLUSION: ART is better than SRT in terms of bRFS and OS, particularly for more aggressive cases, advanced T stage and higher Gleason Score. Postoperative prostate cancer radiotherapy should be applied as soon as possible after surgery. The use of modern techniques such as VMAT-IGRT significantly reduces toxicity.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Resected pN1 non-small cell lung cancer: recurrence patterns and nodal risk factors may suggest selection criteria for post-operative radiotherapy.

PURPOSE: To describe the pattern of recurrence in resected pN1 non-small cell lung cancer (NSCLC) and to identify factors predicting an increased risk of locoregional recurrence (LR) or distant metastasis (DM) to define a selected population who may benefit from postoperative radiotherapy (PORT). METHODS: 285 patients with resected pN1 NSCLC were identified. Patients with positive surgical margins, undergoing neoadjuvant treatment or PORT, were excluded. LR was defined as first event of recurrence at the surgical bed, ipsilateral hilum or mediastinum, and other sites were considered as DM. Kaplan-Meier actuarial estimates of overall survival (OS), progression-free survival (PFS), freedom from LR (FFLR) and freedom from DM (FFDM) in different subgroups were compared with the log-rank test. Multivariate analysis was calculated. RESULTS: 202 patients met the inclusion criteria, 24 % received adjuvant chemotherapy. The median follow-up was 39 months. The total number of recurrences was 118 (64.4 %): 44 (24 %) and 74 (40.4 %) for LR and DM, respectively. Five-year OS and PFS rates were 39.2 and 33.3 %, respectively. Extra capsular extension (ECE) (RR 2.10, p = 0.01) and lymph nodal ratio (LNR) >0:15 (RR 1.68, p = 0.015) were associated with a worse PFS. ECE and LNR >0.15 were significantly related to a worst FFLR (RR 3.04 and 4.42, respectively), and adenocarcinoma to an unfavorable FFDM (RR 1.97, p = 0.013). CONCLUSIONS: Nodal factors as high LNR and ECE can predict an increased risk of worse FFLR and PFS. Prospective data on selected patients, treated with modern radiotherapy techniques, need to be collected to re-evaluate the role of radiotherapy.

External beam radiotherapy ± chemotherapy in the treatment of anal canal cancer: a single-institute long-term experience on 100 patients.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1-4N0-3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3-G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

Randomized, multicenter, phase IIb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin + radiotherapy versus cisplatin + 5-fluorouracil + radiotherapy.

PURPOSE: To prospectively compare the rates of pathologic response, acute toxicity, and sphincter preservation with two different schedules of preoperative chemoradiotherapy in patients with cT3 mid-distal rectal cancer. METHODS AND MATERIALS: Patients with cT3 and/or N+ resectable rectal carcinoma were randomized to receive one of the two following chemoradiotherapy regimens: cisplatin, 5-fluorouracil, and radiotherapy (PLAFUR) or raltitrexed, oxaliplatin, and radiotherapy (TOMOX-RT). For PLAFUR, cisplatin (60 mg/m(2)) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m(2)) on Days 1-4 and 29-32, plus concurrent radiotherapy (50.4 Gy in 1.8-Gy fractions daily). For TOMOX-RT, raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) was given on Days 1, 19, and 38 with the same radiotherapy regimen as used for PLAFUR. Surgery was performed 6-8 weeks after completion of chemoradiotherapy. All pathologic specimens were reviewed by a designated expert pathologist. The primary endpoint of this study was pathologic tumor downstaging (defined as tumor regression grade 1-2). Secondary endpoints included the incidence of ypT0, clinical tumor downstaging, sphincter-saving surgery, and acute treatment-related toxicity. RESULTS: Between 2002 and 2005, 164 patients were accrued in 10 Italian centers, 83 patients in the PLAFUR arm and 81 in the TOMOX-RT arm. Overall, tumor regression grade 1-2 was observed in 76 patients (46.4%) and ypT0 in 49 (29.9%). The tumor regression grade 1-2 rate was 41.0% vs. 51.9% (p = 0.162) and the ypT0 rate was 24.1% vs. 35.8% (p = 0.102) for the PLAFUR vs. TOMOX-RT arm, respectively. The overall rate of tumor regression grade 1 and ypN+ was 4.6%. The occurrence of ypT downstaging was significantly greater in the TOMOX-RT arm (p = 0.035). Grade 3-4 acute toxicity occurred in 19 patients (11.6%): 7.1% in the PLAFUR arm vs. 16.4% in the TOMOX-RT arm. Sphincter-saving surgery was performed in 143 patients (87.2%) overall: 87.9% in the PLAFUR arm and 86.4% in the TOMOX-RT arm. CONCLUSIONS: Compared with the PLAFUR regimen, TOMOX-RT achieved a greater incidence of downstaging but was associated with a correspondingly greater rate of acute Grade 3+ toxicity. With longer follow-up, the local control and survival rates might offer additional guidance as to the choice of regimen.

Integrated treatments for non-small cell lung cancer.

Even a small percent increase in survival rates after treatment for lung cancer can produce a large benefit in terms of absolute numbers of lives saved, due to the very high incidence of the disease. Clinical results after surgery alone or radiotherapy alone are far from being satisfactory. Therefore, the integration of surgery with radiotherapy (both in the preoperative and in the postoperative setting) has been increasingly tested in the clinic. Radio-chemotherapeutic approaches progressively more effective have been developed for patients with inoperable disease, but also in combination with surgery. This review focuses on the current practice and on the ongoing clinical research in this field. The important issue of the short- and long-term toxicity of combined modality treatments in these patients is also emphasized, along with the research efforts for minimizing toxicity, especially as far as radiotherapy is concerned.