Preoperative chemoradiotherapy induces multiple pathways related to anti-tumour immunity in rectal cancer.

BACKGROUND: Rectal cancer treated with preoperative radiotherapy (RT) provides an interesting model to study changes induced on cancer cell immuno-phenotype that could be exploited by immunotherapy interventions to improve prognosis. MATERIALS AND METHODS: We assessed the expression of HLA-class-I, ß2-microglobulin, TAP1, PD-L1 and STING/IFNß in preoperative biopsies and respective post-RT surgical specimens from patients with rectal cancer (n = 27). The effect of radiation was further investigated in colorectal adenocarcinoma cell lines HT-29 and Caco-2. RESULTS: Rectal carcinomas exhibited extensive loss of expression of HLA-Class-I related molecules, which was restored in post-irradiation surgical specimens (P < 0.0001). RT induced the expression of IFNß and STING in cancer cells and tumour-infiltrating lymphocytes (P < 0.0001). In in vitro experiments, irradiation with 4 Gy or 10 Gy induced the expression of HLA-class-I protein (P < 0.001). PD-L1 levels were transiently induced for two days (P < 0.001). cGAS, STING, IFNß and the downstream genes (MX1, MX2, UBE2L6v2, IFI6v2 and IFI44) mRNA levels significantly increased after 3 × 8 Gy or 1 × 20 Gy irradiation (P < 0.001). TREX1 mRNA levels remained unaltered. CONCLUSIONS: RT induces the IFN-type-I pathway and the expression of HLA-class-I molecules on rectal carcinoma. The transient induction of PD-L1 expression suggests that long-course daily RT may sustain increased PD-L1 levels. Anti-PD-L1/PD-1 immunotherapy could block this immunosuppressive pathway.

Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer.

Hyperthermia has the potential to damage cancerous tissue by increasing the body temperature. However, targeting cancer cells whilst protecting the surrounding tissues is often challenging, especially when implemented in clinical practice. In this direction, there are data showing that the combination of nanotechnology and hyperthermia offers more successful penetration of nanoparticles in the tumor environment, thus allowing targeted hyperthermia in the region of interest. At the same time, unlike radiotherapy, the use of non-ionizing radiation makes hyperthermia an attractive therapeutic option. This review summarizes the existing literature regarding the use of hyperthermia and nanoparticles in cancer, with a focus on nanoparticle-induced cytotoxicity mechanisms.

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy.

Phyllodes tumors are rare breast lesions of fibroepithelial origin. Malignant transformation with metastases is linked with poor prognosis. We present a case of a 62-year-old woman with a recurrent malignant phyllodes tumor of the breast and lung metastases. The patient was originally presented with a borderline phyllodes tumor (7.4 cm) of the left breast, treated with wide local excision. A year later, the patient returned with palpable left breast masses. On PET-CT, increased uptake of 18F-FDG by large breast tumors was evident. A right lung lesion of metastatic origin was also present. A simple left breast mastectomy was performed. Histopathological report described 2 malignant phyllodes tumors (7 cm and 6.5 cm). One month later, during the CT simulation for radiotherapy planning, encysted fluid in the chest wall and 2 additional pulmonary lesions of the right lung were identified, confirming progressive lung metastatic disease. Both the chest wall and the regional lymph node area were irradiated with hypofractionated and accelerated radiotherapy. Biweekly chemotherapy with albumin-bound paclitaxel, cisplatin, and liposomal doxorubicin was also prescribed at the start of radiotherapy for 12 cycles. At the end of chemotherapy, complete regression of lung metastases was achieved, and there was no evidence of local recurrence. Within 2 years of follow-up, the patient is free of disease and treatment-related toxicities. Accelerated hypofractionated radiotherapy is effective in the locoregional control of malignant phyllodes tumors. The combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy has acceptable toxicity and is highly effective in eradicating metastatic lesions.

Is Locally Advanced Head-Neck Cancer One More Candidate for Accelerated Hypofractionation?

BACKGROUND/AIM: Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. PATIENTS AND METHODS: We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different HypoAR fractionations (3.5 Gy/day × 14-15 fractions, 2.7 Gy/day × 20-21 fractions, and 2.5 Gy/day × 21-22 fractions). RESULTS: Protraction of the overall treatment time due to oropharyngeal mucositis was enforced in 18/57 laryngeal, 6/19 nasopharyngeal, and 15/48 cancer patients with other tumors. Regarding late toxicities, laryngeal edema grade 3 was noted in 5/57 patients with laryngeal cancer, while severe dysphagia was noted in 4/124 and tracheoesophageal fistula formation in 1/124 patients. The complete response rates obtained were 73%, 84%, and 67% in patients with laryngeal, nasopharyngeal, and other tumors, respectively. The 3-year locoregional progression-free survival was 58%, 73%, and 55%, respectively. CONCLUSION: HypoAR chemoradiotherapy is feasible, with acceptable early and late radiotherapy toxicities, response rates and LPFS.

Complementary Therapies for Patients with Cancer: Reflexology and Relaxation in Integrative Palliative Care. A Randomized Controlled Comparative Study.

Objectives: Comparison of the effects of reflexology and relaxation on pain, anxiety, and depression, and quality of life (QoL) of patients with cancer. Design: A stratified random sample was selected, using an experimental design. Location: An outpatient Palliative Care Unit in Attica, Greece. Subjects: 88 patients suffering with cancer. Interventions: The sample was randomly divided into two equal groups, a reflexology and a relaxation group. The number of interventions for both groups was six 30-min weekly sessions. Outcome measures: The Greek Brief Pain Inventory (G-BPI) was used to measure pain, the Greek Hospital Anxiety and Depression Scale for screening anxiety and depression, and finally the Short Form Health Survey was used to measure QoL. Measurements of the above tools were taken three times in both groups as follows: preintervention, at fourth and at sixth week of intervention. Results: Anxiety and depression for both groups exhibited a statistically significant decrease during the observation period (p < 0.001, η2 > 0.25) but at the sixth week, there was a more significant decrease in the reflexology group compared with the relaxation group (p = 0.062, η2 = 0.044 vs. p = 0.005, η2 = 0.096 for anxiety), (p = 0.006, η2 = 0.094 vs. p = 0.001, η2 = 0.138 for depression). QoL physical and mental component measurements were significantly greater for the reflexology group (p < 0.001, η2 = 0.168 and p = 0.017, η2 = 0.071, respectively). The baseline-to-sixth week G-BPI measurements were markedly decreased for the reflexology group (p = 0.207, η2 = 0.020). Conclusions: Both interventions, relaxation and reflexology, seemed to be effective in decreasing anxiety and depression in patients with cancer. However, reflexology was found to be more effective in improving QoL (physical component) and to have a greater effect on pain management than relaxation.

In vitro effect of hyperthermic Ag and Au Fe3O4 nanoparticles in cancer cells.

PURPOSE: To investigate the anti-cancer efficacy of hyperthermic Ag and Au Fe3O4 core nanoparticles via cytotoxicity study (MTT assay) and the underlying molecular mechanism of action (changes in gene expression via quantitive real time PCR (qRT-PCR). METHODS: HEK293, HCT116, 4T1 and HUH7 human cell lines and 4T1 musculus mammary gland cell line were incubated with Fe3O4 core Ag(Au) shell nanoparticles (NPs) prior to a hyperthermia session. MTT assay was performed to estimate the cytotoxic effects of these NPs. RNA extraction and cDNA synthesis followed so as to quantify mRNA fold change of hsp-70, p53, bcl-2 and casp-3 via qRT-PCR. RESULTS: Fe3O4 core Au shell (concentrations of 400 and 600µg/mL) produced the greatest reduction of viability on HCT116 and 4T1 cells while Fe3O4 core Ag shell (200, 400 and 600µg/mL) reduce viability on HUH7 cells. Hsp-70, p53 and casp-3 were up-regulated while bcl-2 was downregulated in most cases. CONCLUSIONS: Fe3O4 core Ag (Au) shell induced apoptosis on cancer cells (HCT116 and HUH7) via the p53/bcl-2/casp-3 pathway. 4T1 cells also underwent apoptosis via a p53-independent pathway.

Quality of Life, Anxiety, and Depression in the Head-and-Neck Cancer Patients, Undergoing Intensity-Modulated Radiotherapy Treatment.

AIMS: The aim of this study is to investigate and compare distress and quality-of-life parameters among head-and-neck cancer patients who underwent intensity-modulated radiotherapy (IMRT). SUBJECTS AND METHODS: The patients' sample consists of 55 individuals under IMRT treatment. Three questionnaires (Quality of Life Questionnaire [QLQ]-C30 and QLQ-H and N35) of the European Organization for the Research and Treatment of Cancer and the Greek Hospital Anxiety and Depression Scales were used. RESULTS: Functioning and symptoms scales measured a week before the scheduled treatment worsen significantly until the end of the treatment and at the 3-month follow-up, tend to revert to their pretreatment values. CONCLUSIONS: Our results showed that all parameters (functioning scales, symptoms scales, and G-HAD subscales) worsen from the start to the end treatment and tend to revert to their pretreatment values after a 3-month period.

Intraoperative radiation therapy (IORT) in head and neck cancer: A systematic review.

BACKGROUND: Multimodality therapy constitutes the standard treatment of advanced and recurrent head and neck cancer. Since locoregional recurrence comprises a major obstacle in attaining cure, the role of intraoperative radiation therapy (IORT) as an add-on in improving survival and local control of the disease has been investigated. IORT allows delivery of a single tumoricidal dose of radiation to areas of potential residual microscopic disease while minimizing doses to normal tissues. Advantages of IORT include the conformal delivery of a large dose of radiation in an exposed and precisely defined tumor bed, minimizing the risk of a geographic miss creating the potential for subsequent dose reduction of external beam radiation therapy (EBRT). This strategy allows for shortening overall treatment time and dose escalation. The aim of this review is to summarize recent published work on the use of IORT as an adjuvant modality to treat common head and neck cancer in the primary or recurrent setting. METHODS: We searched the Medline, Scopus, Ovid, Cochrane, Embase, and ISI Web of Science databases for articles published from 1980 up to March 2016. RESULTS: Based on relevant publications it appears that including IORT in the multimodal treatment may contribute to improved local control. However, the benefit in overall survival is not so clear. CONCLUSION: IORT seems to be a safe, promising adjunct in the management of head and neck cancer and yet further well organized clinical trials are required to determine its role more precisely.

Splenic irradiation as palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis: a multi-institutional experience.

PURPOSE: To evaluate the impact of splenic irradiation as a palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis. METHODS: Seventeen patients with chronic myelogenous leukemia and 3 with idiopathic polycythaemia presented with splenomegaly, splenic pain and anemia. Due to symptomatic splenomegaly, despite first-line treatment, the patients underwent splenic irradiation. Two patients received two different schedules of external radiotherapy (580 cGy in 5 fractions and 600 cGy in 6 fractions). Eight patients received 980 cGy in 14 fractions. Ten patients received two courses of 360 cGy in 6 fractions, 3 months apart. Median follow-up was 12 months post irradiation. RESULTS: The patients showed excellent response to treatment one month post-radiotherapy, while treatment was well tolerated without severe toxicity. The dimensions of the spleen decreased significantly. Pain-related Visual Analogue Score (VAS) regressed after completion of irradiation. During 12-month follow-up all patients maintained the benefit of radiotherapy. CONCLUSION: This study indicates that splenic irradiation could be a safe and effective palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis.

Reliability and Validity of the Greek Version of Patient Generated-Subjective Global Assessment in Cancer Patients.

The authors sought to determine the reliability and validity of psychometric properties of the Greek Patient-Generated Subjective Global Assessment (PG-SGA) in cancer patients attending a palliative care unit. The scale was translated into Greek. The study took place in an outpatient palliative care unit and 238 cancer patients completed the nutrition assessment. For treatment effect, the index was administered to 164 patients, whereas for the test of the instrument's robustness to 100 patients. Both assessments took place 15 days after the baseline assessment. Ninety-three patients were well-nourished, 104 were moderately malnourished, and 41 were severely malnourished. Reliability was assessed by the internal consistency and test-retest of the instrument. Validity was assessed with construct validity using the PG-SGA items, treatment effect, and criterion validity. Weight loss, physical examination, activities and function, and symptoms were predictors to the classification. Mean values in male patients classified as severely malnourished had the lowest values in all objective parameters except serum albumin, whereas severely malnourished female patients had the lowest values in all objective parameters except serum albumin and arm muscle circumference (AMC). Values of serum transferrin, AMC, and body mass index were significantly lower in patients classified as severely malnourished. The Greek PG-SGA is a psychometrically sound assessment in Greek cancer patients.

Accelerated hypofractionated whole-breast irradiation with concomitant daily boost in early breast cancer.

OBJECTIVES: The aim of this study is to evaluate the feasibility and the related toxicity of hypofractionated whole-breast irradiation with a concomitant daily boost in early breast cancer women not eligible for accelerated partial-breast irradiation. METHODS: Twenty-seven patients received 46 Gy to the whole breast in 20 fractions/4 weeks with 2.3 Gy/fraction plus an additional concomitant daily boost of 0.4 Gy to the tumor bed, giving a total dose of 54 Gy (EQD2=60 Gy). The cosmetic outcome was assessed according to the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group grading system. RESULTS: Three months after the end of radiotherapy, 59.2% and 40.7% of patients showed grade 0 skin toxicity and grade 1 skin toxicity, respectively. After 6 months, 70.4% and 29.6% of patients showed grade 0 and grade 1 skin toxicity. After 1 year, grade 0 skin toxicity was found in 77.7% of the patients and grade 1 skin toxicity in 22.2% of the patients. After 18 months, grade 0 skin toxicity was found in 92.6% and grade 1 skin toxicity in 7.4% of the patients. After a median follow-up of 24 months, all patients showed excellent cosmetic results with minimal breast edema and minimal skin changes. There have been no local relapses to date. CONCLUSION: The accelerated hypofractionated schedule with a concomitant boost appears to be an acceptable alternative to the traditional longer schedule, with low local toxicity and excellent to good short-term cosmetic results, although a much longer follow-up is needed to assess the local control rate.

Caregivers' attachment patterns and their interactions with cancer patients' patterns.

PURPOSE: To provide a brief review of the empirical literature regarding the attachment style of the cancer patients' caregivers as well as the link between attachment, caregiving, and care-receiving behaviors are defined. METHODS: An extensive systematic electronic review (Medline, PsycINFO, and Attachment Theory Website (ATW)) and subsequent examination of reference lists were carried out to retrieve published articles up to 2011, using attachment and cancer in combination with caregiver, spouse, dyad, and family as the key words. The titles, abstracts, or full articles, if necessary, were reviewed to determine whether the articles met the eligibility criteria. RESULTS: Eighty-seven studies have been identified, including research articles, books, and chapters in books. CONCLUSIONS: The attachment style of a caregiver can influence how they respond to a patient's needs. Studies have found that attachment anxiety or avoidance is more likely to interfere with effective and sensitive caregiving.

Challenges and choices in prostate cancer irradiation: from the three dimensional conformal radiotherapy to the era of intensity modulated, image-guided and adaptive radiation treatment.

In the last decades the status of radiotherapy was tremendously increased in terms of conformity to the target as well as image-guided techniques in conjunction with intensity-modulated radiotherapy (IMRT). The technological improvement had a significant clinical outcome for better response and lower toxicity to the surrounding normal tissues. Nowadays the incidence of rectal toxicity has been significantly decreased, especially with image guided radiation therapy (IGRT), whereas the dose escalation to the prostate has driven the clinical practice to the fact that radical radiotherapy for low or intermediate risk prostate cancer is definitely equivalent to surgery. The treatment volume can be reduced by reducing the size of the necessary margins to count for inaccuracies in target position and patient setup. This can be achieved either by improving the daily localization of the target before treatment or by adapting the treatment in response to feedback. This is the goal of image-guided and adaptive radiotherapy, respectively. These techniques improve the accuracy of dose delivery with a significant impact on clinical outcome and toxicity. 

Short-course hypofractionated radiochemotherapy for unresectable locally advanced cancer of the base of tongue: palliation only? A case report and short review of the literature.

We present a case of unresectable cancer of the base of tongue treated with hypofractionated 3D conformal radiotherapy and concomitant chemotherapy. Based on the excellent tumour response in this radiotherapy regimen and international experience in short course treatments we shortly reviewed, we propose that this therapeutic approach could be considered in a curative setting for patients unsuitable for the a standard long course radiochemotherapy schedule.

The impact of intermediate time between chemotherapy and hypofractionated radiotherapy to the radiation induced skin toxicity for breast adjuvant treatment.

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty-four patients with stage I-II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose-EQD2- 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow-up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late-toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.

Suggestion for a new grading scale for radiation induced pneumonitis based on radiological findings of computerized tomography: correlation with clinical and radiotherapeutic parameters in lung cancer patients.

BACKGROUND: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. MATERIALS AND METHODS: The chest CT films of 20 patients with non-small cell lung cancer who have undergone three- dimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. RESULTS: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). CONCLUSIONS: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. MATERIALS AND METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for use of each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. RESULTS: Forty-one papers were reviewed. There was sufficient evidence to recommend the use of benzydamine mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving moderate-dose radiation therapy (up to 50 Gy), without concomitant chemotherapy. A new suggestion was developed against the use of misoprostol mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving radiation therapy. Positive results were reported for some other anti-inflammatory agents. However, no guidelines were able to be developed for any other agents due to insufficient and/or conflicting evidence. CONCLUSIONS: The use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. Additional well-designed studies are needed to examine the use of this class of agents for oral mucositis.

Comparison of two radiotherapeutic hypofractionated schedules in the application of tumor bed boost.

AIM: Evaluation of related radiation toxicity and efficacy in terms of local control of 2 radiotherapeutic hypofractionated schedules in the application of tumor bed boost by using 2 different planning techniques. METHOD: Eighty-one patients with stage I-II disease were retrospectively selected with either concomitant (group A) or sequential (group B) boost for the tumor bed. In group A, 27 patients were treated with a total dose of 46 Gy to the whole breast and 54 Gy to the tumor bed in 20 concomitant fractions. In group B, 54 patients were treated with a total dose of 42.4 Gy in 16 fractions to the whole breast and 53 Gy to the tumor bed by 4 sequential fractions. The boost was administered with multiple photon-beam fields. The median follow-up time was 24 months. RESULTS: The statistical analysis for the 2 groups of the study showed that skin toxicity was significantly worse in group A (P < .05, Kruskal-Wallis H test). For groups A and B at the completion of radiation therapy, grade 1 skin toxicity was observed in 18/27 patients (66.6%) and 13/54 patients (24.1%), respectively, whereas grade 2/3 was observed in 9/27 patients (33.3%) vs. 5/54 patients (9.3%), respectively (P < .001). One year after irradiation, in group A and in group B, the skin toxicity was of grade 1 in 6/27 patients (22.2%) vs. 2/54 patients (3.7%), respectively (P = .008). Within 2 years, the breast returned to its original form in all patients. No patient showed local disease recurrence. CONCLUSIONS: The accelerated hypofractionated schedules in the application of the tumor bed boost by using the 2 different planning techniques appears to be effective and well tolerated.

Systematic review of amifostine for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. RESULTS: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. CONCLUSION: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.

Male breast carcinoma: epidemiology, risk factors and current therapeutic approaches.

Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.