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.
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.
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).
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.
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.
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.
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 8
Rome INTER-MEETING (INTERventional Radiotherapy Multidisciplinary Meeting), June 24
, 2017. The present paper describes the final results of the survey and possible future teaching strategies resulting from the discussion.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
to assess the prognostic role in recurrence and survival of perineural invasion (PNI) in vulvar squamous cell cancer (VSCC).
Patients underwent primary surgery for VSCC from January 2009 to December ...2016 served as the study cohort. We collected demographic, clinical, pathological characteristics and follow-up data, and we compared them among PNI-negative versus -positivepatients. We calculated disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier and univariate log-rank test. We conducted a multivariate analysis with cox-proportional hazard models for DFS and OS, including age, tumor size, depth of invasion, free tumor margin <8 mm, high-grade histology, lymph vascular space invasion, PNI, extracapsular lymph nodal disease, lymph nodal ratio >0.2 and FIGO Stage 2009 (Early I-II versus Advanced III-IV).
We found 74 patients with a PNI prevalence of 31.1%. The 5-year DFS was favourable for PNI-negative patients (72% versus 18%; p = 0.00). The 5-year OS was 75% versus 35% in favor of PNI-negative patients (p = 0.00). The subgroup analysis conducted among stage confirmed a decreased DFS and OS in PNI-positive patients. Multivariate analysis showed that PNI (HR 2.74; CI95% 1.10–7.13; p = 0.03) and extracapsular lymph nodal disease (HR 13.54; CI95% 2.87–64.07; p = 0.01) are independent prognostic factors for earlier recurrence. OS was significantly reduced in case of PNI (HR 4.93; CI95% 1.33–18.35; p = 0.01) and extracapsular lymph nodal disease (HR 10.63; CI95% 1.65–68.57; p = 0.01).
PNI is an independent prognostic factor for aggressive behavior and unfavorable course in VSCC and should be considered in adjuvant treatment planning.
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.
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.
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