Low-dose radiation therapy for hand osteoarthritis: shaking hands again?

BACKGROUND: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. MATERIALS AND METHODS: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. RESULTS: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed. CONCLUSION: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.

5-year results of accelerated partial breast irradiation (APBI) with SBRT (stereotactic body radiation therapy) and exactrac adaptive gating (Novalis®) for very early breast cancer patients: was it all worth it?

PURPOSE: To explore the feasibility of image-guided and respiratory-gated Stereotactic Body Radiation Therapy (SBRT) for Accelerated Partial Breast Irradiation (APBI) in patients with very early breast cancer. MATERIAL AND METHODS: Selected patients with early breast carcinoma after breast-conserving surgery were enrolled in this phase II trial. A fiducial marker was percutaneously placed close to surgical bed and five external fiducials were set on the skin. A CT scan for planning was acquired at free breathing. The treatment was planned and DVH were assessed according to international recommendations. Prescription dose was 30 Gy in five consecutive fractions of 6 Gy. A 6MV monoenergetic LINAC (linear accelerator) that combines stereoscopic X-ray imaging system and ExacTrac Adaptive Gating technique was used. PTV (planning target volume) intrafraction motion was controlled and PTV was irradiated in a selected gated area of the respiratory cycle. Shifts for a correct, gated set-up were calculated and automatically applied. RESULTS: Between April 2013 and October 2015, a total of 23 patients were included. The median tumor size was 12 mm. The mean PTV volume was 114 cc. The mean ipsilateral lung V9 Gy was 2.2% and for left-sided breast cancers, the volume of the heart receiving 1.5 Gy was 11.5%. Maximum skin dose was 30.8 Gy. Acute toxicity was grade1 in all the patients and 100% experienced excellent/good breast cosmesis outcomes. With a median follow-up of 66 months (range 8-99 months) local-relapse-free-survival reaches 100%. One patient developed a second breast cancer outside the treated quadrant after 25.1 months. CONCLUSION: APBI with SBRT and ExacTrac Adaptive Gating System was feasible. The acute and late toxicities were almost null and cosmesis was excellent. We also found that the margins of 5 mm applied from CTV to PTV were sufficient to compensate for geometric uncertainties.

Moderate hypofractionated post-prostatectomy radiation therapy is feasible and well tolerated: experience from a single tertiary cancer centre.

PURPOSE: Conventional post-prostatectomy radiation therapy comprises 6.5-8 weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule MATERIALS AND METHODS: From Oct 2015-Mar 2020, 113 patients, median age of 62 years-old (range 45-76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5 Gy in 2.5 Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy. RESULTS: With a median follow-up of 29 months (range 3-60 months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3 years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments. CONCLUSIONS: Hypofractionated radiotherapy (62.5 Gy in 25 2.5 Gy fractions) is feasible and well tolerated with low complication rates allowing for a moderate dose-escalation that offers encouraging clinical results for biochemical control and survival in patients with prostate cancer after radical prostatectomy.

Retroperitoneal soft-tissue sarcomas: Radiotherapy experience from a tertiary cancer center and review of current evidence.

BACKGROUND: Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy. PATIENTS AND METHODS: We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months (2-114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2. CONCLUSIONS: Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.

A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer.

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

Relationship of serum testosterone, sperm production, and testis traits with fertility of Mangalarga Marchador stallions / Relación entre testosterona sérica, producción espermática y características testiculares con la fertilidad en sementales Mangalarga Marchador / Relação entre testosterona sérica, produção espermática e características testiculares com fertilidade em garanhões Mangalarga Marchador

Abstract Background: Assessing breeding soundness is important to predict the potential fertility of stallions. Objective: To investigate the association of testis traits, total number of spermatozoa, and testosterone with fertility of Mangalarga Marchador breed stallions. Methods: The traits measured were testicular length, width and height, right and left testicular volume and total testicular volume. We also evaluated the total number of spermatozoa (TNS), serum testosterone concentration and fertility of stallions (by embryo recovery from donor mares) in the breeding and non-breeding seasons during 1 year. Analysis of variance was performed to verify the effects of age category (AC; young/adult) and reproductive season on the traits. Correlations and repeatability of the traits were also calculated. Results: The AC did not influence testis traits (p>0.05). Reproduction season affected left testicular length, left testicular height, right testicular width and height (p<0.05). The AC and season affected testis volume (p<0.05). There were no effects of AC and season on TNS and testosterone (p>0.05). We observed strong correlations between all testicular measurements and testicular volume (0.53 to 0.75), medium correlation between TNS and testis volume (0.32), and low correlation between testosterone and testis traits (0.20). Repeatability of the characteristics of left and right testis was medium to high (0.22 to 0.78). Embryo recovery rate was 60% and its correlation with TNS was 0.44. Conclusion: Testis size evaluation is recommended over the evaluation of serum testosterone concentration to predict sperm output. Sperm output (TNS) is a good predictor of stallion fertility.

Resumen Antecedentes: Es importante realizar examen andrológico de sementales para predecir su potencial reproductivo. Objetivo: Evaluar la asociación entre características testiculares, número total de espermatozoides y testosterona con la fertilidad de sementales de raza Mangalarga Marchador. Métodos: Las características medidas fueron: longitud testicular, ancho y altura del testículo. También fue calculado el volumen testicular derecho, izquierdo y total, así como el número total de espermatozoides (TNS), concentración sérica de testosterona y fertilidad (por recuperación embrionaria de las yeguas) de los sementales dentro y fuera de la temporada reproductiva durante un año. Se realizó análisis de varianza para evaluar el efecto de categoría de edad (AC) y estación reproductiva sobre las características. Resultados: La AC no influenció las características testiculares (p>0,05). La estación reproductiva influenció la longitud del testículo izquierdo, la altura del testículo izquierdo, y el ancho y altura del testículo derecho (p<0,05). La AC y la estación reproductiva influenciaron el volumen testicular (p<0,05). No hubo efecto de AC y estación reproductiva en el TNS y testosterona (p>0,05). Se observó una alta correlación entre todas las características testiculares y el volumen testicular (0,53 a 0,75), mediana correlación entre TNS y el volumen testicular (0,32), y una baja correlación entre las medidas testiculares y la testosterona (0,20). La repetitividad de las medidas testiculares fue media a alta (0,22 a 0,78). La tasa de recuperación embrionaria fue de 60% y la correlación con TNS fue 0,44. Conclusión: Para predecir la producción espermática se recomienda evaluar las características testiculares, sin necesidad de medir testosterona. La producción espermática es un buen predictor de la fertilidad de los sementales.

Resumo Antecedentes: Realizar o exame andrológico no garanhão, é importante para predizer seu potencial reprodutivo. Objetivo: Avaliar a associação das características testiculares, número total de espermatozoides, testosterona e fertilidade de garanhões Mangalarga Marchador. Métodos: As características mensuradas foram: comprimento do testículo, largura do testículo e altura do testículo. Também foi calculado o volume testicular, direito, esquerdo e total, assim como calculado o número total de espermatozoides (TNS), concentração sérica de testosterona e fertilidade dos garanhões (pela recuperação embrionária das éguas doadoras) durante e fora da estação reprodutiva durante um ano. Foi feita análise de variância para verificar efeito da categoria de idade (AC) e estação reprodutiva sobre as características. Resultados: A AC não influenciou nas características testiculares (p>0,05). Estação reprodutiva influenciou no comprimento testicular esquerdo, altura testicular esquerda, largura e altura testicular direita (p<0,05).A AC e estação reprodutiva influenciaram no volume testicular (p<0,05). Não houve efeito da AC e estação reprodutiva no TNS e testosterona (p>0,05). Foi observado alta correlação entre todas características testiculares e volume testicular (0,53 a 0,75), media correlação entre TNS e volume testicular (0,32), e baixa correlação entre medidas testiculares e testosterona (0,20). A repetitividade das medidas testiculares foi meia a altas (0,22-0,78). A taxa de recuperação embrionária foi 60% e a correlação com TNS foi de 0,44. Conclusão: É recomendada a avaliação das características testiculares para predizer a produção espermática sem necessidade de mensurar testosterona. A produção espermática é um bom preditor da fertilidade dos garanhões.

Management of unresectable, locally advanced pancreatic adenocarcinoma.

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

Adjuvant treatment for pancreatic ductal carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a very poor prognosis. Most of the patients are diagnosed in advanced stages of the disease, and 5-year survival rates in these patients remains <10%. Surgery still remains the only radical treatment option, although only 15-20% of patients are candidates for surgical resection at the time of the diagnosis. Patients who undergo radical surgery still have a limited survival rate, being the average of 23 months. Three clinical trials have shown that adjuvant chemotherapy therapy after surgery may improve survival: CONKO-1, ESPAC-3, and ESPAC-4. Adjuvant therapy is recommended in patients with R0/R1, T1-4/N1-0 tumors and with ECOG 0-1. In patients with ECOG-2, the decision needs to be individualized. Treatment schemes that have demonstrated efficacy include gemcitabine alone, 5-fluorouracil, or the combination of gemcitabine and capecitabine for six months. Prior to adjuvant treatment, the following test are recommended: Complete blood tests, including CA19.9 biomarker; imaging studies to rule out early disease relapse (preferable thorax-abdomen-pelvic CT). Studies that have evaluated the efficacy of radiation therapy in the adjuvant setting have presented conflicting results. Its use should be considered in patients with R1 or R2 tumors or in those with lymph nodes involved.

Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain.

The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.

A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer.

A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA.