Purpose
Patient-reported outcome measures can be useful to assess symptoms in head and neck cancer (HNC) patients treated with radio-chemotherapy. This is a pilot study on the VHNSS-IT (the Italian ...version of the Vanderbilt head and neck symptom survey) performed to assess both the feasibility and utility of its administration in clinical practice.
Methods
The outcomes analyzed were feasibility to recruit patients, feasibility to complete the questionnaire, feasibility to review the questionnaire, utility perceived by clinicians, distribution of patient’s answers reflecting symptom’s intensity.
Results
Among the 38 patients enrolled, 37 completed the VHNSS-IT (refusal rate 2.6%). Median time of completion was 6′57″. Time of completion was influenced by age (
p
= 0.002), grade of education (
p
= 0.023) and employment status (
p
= 0.004). Time after the start of the radiotherapy course (< 6 months vs. > 6 months) and surgery (yes vs. no) influenced symptoms’ intensity. Median time for review was 2′15″. Time burden was perceived to be acceptable for all clinicians; they all also found the questionnaire easy to use. Rates of global perceived utility and future intention to use the questionnaire were 100%.
Conclusions
The VHNSS-IT has demonstrated to be a useful measurement of symptoms’ burden for patients with HNC. The survey can be easily completed during the clinic routine without interfering with doctors’ visits schedule, and it can help healthcare providers to identify symptoms that require referral, education or intervention.
Background and purpose: Two previous “Patterns Of Practice” surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy ...(EBRT) between 1980 and 2003, established a “benchmark” Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. Results: More than 50% of POP III patients were classified as low or intermediate risk using D’Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004–2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT—allowing for tighter margins—would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies.
In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) ...in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling.
The aim of the study is to evaluate clinical features and outcomes after different therapeutic strategies for ductal prostate adenocarcinoma (DPC), a rare but aggressive subtype of invasive prostate ...cancer (PCa) accounting for, in the pure and mixed form, 1% or less and 5% or less, respectively, of all the newly diagnosed PCa.
Patients with a proven diagnosis of DPC undergoing surgery, radiotherapy, and androgen deprivation therapy, alone or in combination, were considered for this multicenter, retrospective study. The study assessed overall survival (OS), disease-free survival (DFS), and age-related disease-specific survival.
Eighty-one patients met the study inclusion criteria. Pure DPC was found in 29 patients (36%) and mixed ductal-acinar-PCa in 52 patients (64%). After a median follow-up of 63 months (range, 3-206 months), 3- and 5-year OS rates were 84% and 67%, respectively, and 3- and 5-year DFS rates were 54% and 34%, respectively. There were no significant differences in OS or DFS between the pure and mixed DPC groups. Pure DPC was associated with a higher rate of metastatic disease at onset. Patients 74 years or younger had better disease-specific survival (
=0.0019). A subgroup analysis favored radiotherapy as the primary treatment for nonmetastatic, organ-confined DPC (3- and 5-year DFS of 80% and 50%, respectively, compared with 5-year DFS of 35% for surgical patients;
= 0.023).
Our study found DPC to be rarer, more aggressive, more likely to metastasize, and have a worse prognosis than the common acinar variant, especially in its pure form. Multicenter series are encouraged to obtain large data sets, or propensity score matching analyses with patients with conventional PCa are desirable to understand the best therapeutic approach and improve outcomes.
Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions ...of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.
We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. ...Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.
Radiotherapy is one of the standard treatments for cutaneous lymphoma and Total Skin Electrons Beam Irradiation (TSEBI) is generally used to treat diffuse cutaneous lymphoma and some cases of ...localized disease. Helical IMRT (HI) allows to treat complex target with optimal dose distribution and organ at risk sparing, so helical tomotherapy has been proposed as alternative technique to TSEBI but only one preliminary report has been published.
Three patients treated (from May 2013 to December 2014) with Helical IMRT, with a total dose between 24 and 30 Gy, were retrospectively evaluated. Data about dosimetric features, response and acute toxicity were registered and analyzed. Planned target coverage was compared with daily in vivo measures and dose calculation based on volumetric images used for set up evaluation as well.
The patients had a mean measured surface fraction dose ranging from 1.54 Gy up to 2.0 Gy. A planned target dose ranging from 85 to 120% of prescription doses was obtained. All doses to Organs At Risk were within the required constraints. Particular attention was posed on "whole bone marrow" planned V
, V
and V
values, ranging respectively between 23 and 43%, 20.1 and 38% and 9.8 and 24%. A comparison with the theoretical homologous values obtained with TSEBI has shown much lower values with TSEBI. Even if treatment was given in sequence to the skin of the upper and lower hemi-body, all the patients had anaemia, requiring blood transfusions, leukopenia and thrombocytopenia.
Based on our limited results TSEBI should still be considered the standard method to treat total skin because of its pattern of acute and late toxicities and the dose distribution. In this particular case the better target coverage obtained with HI can be paid in terms of worse toxicity. Helical IMRT can instead be considered optimal in treating large, convex, cutaneous areas where it is difficult to use multiple electrons fields in relation with the clinical results and the limited and reversible toxicities.
Background: Stereotactic Radiotherapy (SRT) in pancreatic and biliary tract cancer (PBC) suffers from proximity to any organ(s) at risk (OARs). Some strategies to manage this issue have previously ...been proposed, such as Simultaneous Integrated Protection (SIP), with the aim of maintaining a biological effective dose prescription while reducing toxicities. We performed a systematic review of the literature about SRT techniques applied in patients with tumor in proximity to OARs, with the aim of testing safety and efficacy. Methods: using PRISMA guidelines, we selected studies from a pool of more than 25,000 articles published from 2010 to 30 January 2023 that explored the use of SRT to deliver targeted treatment for PBC. We then selected the ones referring to decreases in prescription doses (for SRT only) in the area of overlap between planning target volume (PTV) and OARs. Local control (LC) and toxicities being detailed were exclusion criteria for articles. Results: 9 studies were included in our review, considering 368 patients. One-year LC probability ranges between 67% and 98.3% were reported. Late G3 toxicities ranged between 0% and 5.3%, while G4-G5 late toxicities were both reported as 0.3%. Conclusion: prioritizing critical OAR constraints limits severe toxicities while preserving LC in PBC SRT. Improving in-study reporting is essential to confirm these promising results.
Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized ...prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.
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.
PDF
