Tomotherapy concomitant with cetuximab, followed by cetuximab as single-agent therapy for unresectable squamous cell carcinoma of the skin: a case report.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the second most frequency of all skin tumors. Incidence of SCC has risen significantly due to an increased sun exposure and the number of immunodeficient patients. Cutaneous SCC is characterized by high Epidermal growth factor receptor (EGFR) expression with low frequency of RAS mutations. Generally, locoregional surgery is curative and systemic therapy is not indicated. We evaluated the activity and toxicity profile of tomotherapy concomitant with Cetuximab, followed by Cetuximab as single agent therapy in a patient affected by unresectable, locally advanced cutaneous SCC. CASE PRESENTATION: At our institution, on March 2012 we treated a 45 years-old patient affected by locally advanced, unresectable G1 SCC of the lumbar region. At our first observation, the patient was asthenic, with severe pain and functional limitations. There was also a superinfection due to Pseudomonas Aeruginosa resistant to antibiotics, and a G3 anemia secondary to the bleeding lesion. ECOG Performance Status was 2. Tomotherapy has been performed concomitant with the Cetuximab (400 mg/m2, followed by weekly doses of 250 mg/m2) at the total dose of 60 Gy (2 Gy/fx), followed by Cetuximab monotherapy.The lesion reduced progressively until disappear even after the suspension of the treatment and the patient achieved complete response. Toxicity resulted in G1 cutaneous rash and G2 toxicity to the nails, appeared after 5 months of treatment, typical toxicity profile of the anti-EGFR therapies. After one month of therapy the Pseudomonas Aeruginosa superinfection totally disappeared. Quality of life resulted significantly improved with reduction until discontinuation of the anti-pain drugs, and progressive increase of the hemoglobin levels. At follow up of 15 months there was no evidence of active disease and the ECOG Performance Status was 0 (zero). CONCLUSION: The treatment was effective and feasible. Considering these excellent results, further studies about concomitant tomotherapy with Cetuximab for advanced/inoperable SCC of the skin are needed.

Reirradiation of Locally Recurrent Prostate Cancer with Cyberknife® System or Volumetric Modulated Arc Therapy (VMAT) and IGRT-Clarity®: Outcomes, Toxicities and Dosimetric Evaluation.

The management of prostate cancer recurrence following external beam radiotherapy is not defined yet. Stereotaxic body reirradiation therapy showed encouraging results for local and biochemical control. From April 2017 to December 2020, 29 patients with prostate cancer recurrence were collected, joining the retrospective studies CyPro (prot. 46/19 OSS) and CLARO (Prot. 19/20 OSS) trials. Patients received Cyberknife® treatment (17 pts) or alternatively VMAT (Volumetric Modulated Arc Technique) therapy by IGRT (Image-Guided Radiation Therapy)/Clarity® (12 pts). By comparing the reirradiation of two groups, urinary (GU), rectal (GI) toxicities, and biochemical control were investigated. Further, the two techniques were dosimetrically compared by rival plans. The VMAT-IGRT Clarity® treatments were replanned with an optimized template developed for prostate VMAT-SBRT in FFF mode keeping the same dose and fractionation scheduled for Cyberknife Group (30 Gy in 5 fx, at 80% isodose). In the CK group, 23% of patients experienced grade 2 acute GU, while 6% grade 2 acute GI. In the VMAT-Clarity® group, acute GU toxicity was recorded in 17%, while for 8% grade 2 late toxicity was recorded. The dosimetric analysis shows that the VMAT-FFF allows to deliver a biological equivalent dose to CK, with the advantage of reducing the likelihood of toxicities arising.

Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients' outcomes are still unclear.

Multimodality treatment of locally advanced soft-tissue sarcomas of the extremities.

BACKGROUND: Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment of locally advanced soft tissues sarcomas of the extremities. Moreover the employment of combined modalities in locally advanced soft tissues sarcomas of the extremities allow to maximize the chance of local cure even in difficult presentation cases, and possibly improve survival, especially in high-risk disease patients. In patients with sarcomas of the extremities in which definitive surgery has not been radical (with positive or "close" margins) radiotherapy can improve the results in terms of Disease Free Survival (DFS) and, together with chemotherapy, of Overall Survival (OS). We recommend radiotherapy in case of deep tumor location, inadequate surgical margins and grade 3 tumour; for positive or "marginal (or close)" excision (that means inadequate surgery) or in selected patients with a bad prognosis, we believe that a multidisciplinary approach can be preferable. INTRODUCTION: Adjuvant radiotherapy (RTE) still has a fundamental role as a post-operative treatment. In patients with sarcomas of the extremities in whom definitive surgery has been or not radical (positive or "close" margins), radiotherapy with chemotherapy can improve the results in terms of Disease Free Survival (DFS) and Overall Survival (OS), while RTE alone seems to improve local control. MATERIALS AND METHODS: From 1/2000 to 12/2005 we treated 34 patients affected by locally advanced sarcomas of the upper or lower extremities with radiotherapy (doses ranging from 54 to 66 Gy) and chemotherapy in 18/34 with an adjuvant scheme that consisted in Epirubicine (120 mg/m(2)) plus Ifosfamide (7000-9000 mg/m(2)). RESULTS: Disease Free Survival (DFS) and the Overall Survival (OS) rates were 76% and 82%, respectively. Eighteen patients developed one or more long-term side effects. Most of these complications were mild: all patients experienced only erithema, edema, local sclerosis or moderate pain. CONCLUSION: Radiotherapy has an important role as a post-operative treatment also when surgery was non-radical. It improves local control more in patients with high-grade sarcomas of the extremity with positive or close margins. It is still difficult to assess the role of adjuvant chemotherapy.

Radiosurgery and stereotactic radiotherapy with cyberknife system for meningioma treatment.

Objective The aim of this work was to evaluate the impact of stereotactic radiosurgery/fractionated stereotactic radiotherapy with the Cyberknife system on local disease control, clinical outcome and toxicity in patients with meningioma, according to the site and histological grade of lesion. From January 2013 to April 2017, 52 patients with intracranial meningiomas were treated with the Cyberknife system. Twenty-four patients had undergone previous surgery: 38% gross total resection, 10% subtotal resection; 27 patients underwent no surgery; 22 patients had a recurrence of meningioma. Methods Radiosurgery was used for lesions smaller than 2 cm, stereotactic radiotherapy for lesions larger than 2 cm, or smaller but close to a critical site such as the optical chiasm, optic pathway or brainstem. Results Local control and clinical outcomes were analysed. Median follow-up was 20 months: six patients died, one after re-surgery died from post-surgical sepsis, three from heart disease. Progression-free survival had a mean value of 38.3 months and overall survival of 41.6 months. We evaluated at 12 months 28 patients (100% local control); at 24 months 19 patients (89% local control); at 36 months nine patients (89% local control). At baseline, 44/52 patients (85%) were symptomatic: 19 visual disorders, 17 motor disorders, six hearing disorders, 10 headache and six epilepsy. Visual symptoms remained unchanged in 52%, improved in 32%, resolved in 16%. Headache was improved in 40%, resolved in 10%, unchanged in 50%. Epilepsy was resolved in 17%, unchanged in 33%, worsened in 33%. Conclusions Stereotactic radiosurgery/fractionated stereotactic radiotherapy with Cyberknife provides a good local disease control, improving visual, hearing and motor symptoms.

Rectal/urinary toxicity after hypofractionated vs conventional radiotherapy in low/intermediate risk localized prostate cancer: systematic review and meta analysis.

PURPOSE: The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. METHODS: PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. RESULTS: The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. CONCLUSIONS: Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.

Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients.

Hypofractionated breast cancer radiotherapy. Helical tomotherapy in supine position or classic 3D-conformal radiotherapy in prone position: which is better?

We propose a comparative dosimetric study of whole-breast hypofractionated radiation therapy using helical tomotherapy (HT) in supine position and 3-D conformal radiotherapy (3D-CRT) in prone position. Twelve patients undergoing breast-conserving therapy were retrospectively selected from October to December 2012. Specific dose-volume parameters were selected for the study. The target coverage was adequate in all patients for both techniques. Significant differences in lung dose distribution were observed: maximum dose (mean value over the 12 plans) was 23.41 Gy in HT plans and 6.65 Gy in 3D-CRT; V20 (i.e. the lung volume receiving 20 Gy) was 0.31% in HT plans and 0.0% in 3D-CRT plans. The mean dose to the heart was 5.57 Gy and 0.93 Gy, respectively. The differences between the two techniques were significant (p<0.05) only for some parameters. We noted better results in the prone position, but with HT, dose constraints were mentioned for the whole set of considered organs.

Non small-cell lung cancer with metastasis to thigh muscle and mandible: two case reports.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death in Europe and the US. Isolated metastases to skeletal muscle and the mandible are very uncommon. CASE PRESENTATION: This report presents two cases. Case 1 concerns a 45-year-old Caucasian woman affected by muscle metastasis of the right thigh from non-small-cell lung cancer. Case 2 concerns a 61-year-old Caucasian man affected by mandible metastasis from non-small-cell lung cancer. Both metastases were detected by diagnostic imaging studies. Both patients were treated with radiation therapy with palliative and antalgic intent. CONCLUSION: Radiation therapy was effective and well tolerated in both cases. Both our patients are alive, with follow-up of 18 months and five months, respectively.

Solitary plasmacytoma of the larynx treated with radiotherapy: a case report.

AIMS AND BACKGROUND: Solitary plasmacytomas are rare tumors accounting for less than 10% of plasma cell neoplasms. On initial presentation they must be differentiated from multiple myeloma. This can be difficult because a high percentage of these tumors may be associated with subsequent development of multiple myeloma. We present a case of plasmacytoma of the larynx treated with surgery and radiotherapy. CASE REPORT: A 56-year-old man presented a solitary plasmacytoma of the larynx. The diagnosis was made by biopsy and the presence of a mass on the right side of the larynx was confirmed by computed tomography and whole-body positron-emission tomography. Soon after the biopsy the patient underwent a CO2 laser cordectomy. After the definitive histological confirmation, the patient was referred to our department for three-dimensional conformal radiotherapy (3DCRT) to the involved site with curative intent. The prescribed dose was 50 Gy. RESULTS: Five months after the 3DRTE treatment there was no CT or PET evidence of tumor, and examination by the otorhinolaryngologist confirmed the success of laser cordectomy and 3DRTE treatment. There were no long-term side effects of the treatment. CONCLUSION: Radiation therapy following CO2 laser cordectomy can achieve excellent locoregional control of solitary plasmacytoma of the larynx.

Prevention of cutaneous damages induced by radiotherapy in breast cancer: an institutional experience.

BACKGROUND AND AIMS: A minimal part of patients treated with radiotherapy on the entire breast may present an acute, subacute or chronic cutaneous damage of the healthy tissues involved in the radiation fields. The aim of this retrospective study was to evaluate the most efficient topical hydrating treatment in the prevention of cutaneous radio-induced acute effects in breast cancer. MATERIAL AND METHODS: From February 2009 to March 2010, 100 patients affected by breast cancer have been recruited, all of the female sex and with an average age of 47 years. The following topical treatments were compared: Pure vitamin E (Vea lipogel®), Omega-3,6,9 (Quinovit®), Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A.s-I-M.t-O.dij, (Ixoderm®), natural triglycerides-fitosterols (Xderit®). All enrolled patients were subjected to breast conservative treatment (quadrantectomy with or without homolateral axillary dissection) and without prosthesis positioning, in combination or not with hormonal treatment. Evaluation of the cutaneous acute toxicity was defined according to the RTOG scale either during radiotherapy and during follow-up (3 months after radiation treatment). RESULTS: All patients completed the radiotherapy; 62% of patients presented G0-G1 cutaneous toxicity, 28% have developed G2 cutaneous toxicity, 10% have developed G3 toxicity; no patient presented G4 toxicity. Analysis of the data revealed a correlation between the topical treatment used and the incidence of cutaneous toxicity. CONCLUSIONS: Of the patients who used the cutaneous hydrating creams--betaglucan, sodium hyaluronate (Neoviderm®) and Vitis vinifera A.s-I-M.t-O.dij (Ixoderm®)--during the radiation treatment, 80% developed G0-G1 toxicity and 20% G2 toxicity. The patients who used the other hydrating creams tested in the study manifested not only G1-G2 toxicity but also some G3 toxicity. Chemotherapeutic treatment with taxanes and/or anthracyclines did not result in an increased breast cutaneous toxicity induced by radiotherapy. The hormone therapy given to patients undergoing radiotherapy did not result in increased breast cutaneous toxicity. Further analysis on a larger number of patients is necessary for definitive results.