Online Adaptive Magnetic Resonance-guided Radiation Therapy for Gynaecological Cancers: Preliminary Results of Feasibility and Outcome.

AIMS: To present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. MATERIALS AND METHODS: Twelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. RESULTS: The median age was 56.5 years (range 31-86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1-42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10-87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45-50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20-50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26-28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. CONCLUSION: MRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible.

Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-institutional Registry Study-IMET, Protocol MF 14-02.

BACKGROUND: One fourth of early-stage breast cancer cases become metastatic during the follow-up period. Limited metastasis is a metastatic disease condition in which the number of metastatic sites and the extent of the disease both are limited, and the disease is amenable to metastatic intervention. This prospective study aimed to evaluate intervention for limited metastases in the lung, liver, or both. METHODS: The study enrolled luminal A/B and/or human epidermal growth factor receptor 2 (HER2)-neu+ patients with operable lung and/or liver metastases in the follow-up assessment after completion of primary breast cancer treatment and patients with a diagnosis of metastasis after 2014. Demographic, clinical, tumor-specific, and metastasis detection-free interval (MDFI) data were collected. Bone metastasis in addition to lung and liver metastases also was included in the analysis. The patients were divided into two groups according to the method of treatment for metastases: systemic therapy alone (ST) group or intervention (IT) group. RESULTS: Until June 2020, 200 patients were enrolled in the study. The demographic data were similar between the two groups. The median follow-up time was 77 months (range 55-107 months) in the IT group (n = 119; 59.5%) and 57 months (range 39-84) in the ST-only group (n = 81; 40.5%). The median MDFI was 40 months (range 23-70 months) in the IT group, and 35 months (range 13-61 months) in the ST-only group (p = 0.47). The groups had similar surgeries for the primary tumor and axilla. Most of the patients had liver metastases (49.5%, n = 99), and 42% (n = 84) of the patients had lung metastases. Both lung and liver metastases were found in 8.5% (n = 17) of the patients. The primary tumor was estrogen receptor/progesterone receptor-positive in 75% (n = 150) of the patients, and 32% (n = 64) of the patients had HER2-neu+ tumors. Metastatic-site resection was performed for 32% (n = 64) of the patients, and 27.5% (n = 55) of the patients underwent metastatic ablative interventions. In the Kaplan-Meier survival analysis, the hazard of death (HoD) was 56% lower in the IT group than in the ST-only group (hazard ratio [HR], 0.44; 95% confidence interval [CI] 0.26-0.72; p = 0.001). The HoD was lower in the IT group than in the ST-only group for the patients younger than 55 years (HR, 0.32; 95% CI 0.17-0.62; p = 0.0007). In the multivariable Cox regression model, HoD was significantly lower for the patients who underwent intervention for metastases and had an MDFI longer than 24 months, but their liver metastases doubled the risk of death compared with lung metastases. CONCLUSION: Metastasis-directed interventions have reduced the risk of death for patients with limited lung/liver metastases who are amenable to interventions after completion of primary cancer treatment. For a select group of patients, such as those with luminal A/B or HER2-neu+ breast cancer who are younger than 55 years with limited metastases to the lung and liver or an MDFI longer than 24 months, surgical or ablative therapy for metastases should be considered and discussed on tumor boards.

An unusual case of mammary gland-like carcinoma of vulva: case report and review of literature.

INTRODUCTION: Accessory breast tissue is a very rare finding in the general population with an incidence of one to two percent. An even rarer occurrence is accessory mammary-like tissue which developed breast carcinoma. The authors present a case of aggressive and metastatic carcinoma of vulvar originating from mammary-like tissue. CASE: A 73-year-old Caucasian female presented with a lesion in her left vulva. The lesion was ulcerated and fragile. A dermatologist had evaluated the lesion and took a punch biopsy. Result was vulvar carcinoma. She was admitted to the gynecologic oncology clinic then after and was operated. After a radical vulvectomy and bilateral inguinal lymphadenectomy she received adjuvant radiotherapy because of lymph node metastasis. One year after the finish of radiotherapy patient was found to have lung and femur metastasis. She began to receive systemic chemotherapy for metastasis. CONCLUSION: Primary mammary-like adenocarcinoma of the vulva is exceedingly rare. There is no consensus about the diagnosis, treatment, and follow up of these patients in literature. However, given that histological data confirms these cancers are behaving like breast cancers instead of known patterns of vulva cancer, the best treatment practices for breast cancer may be applied to treat these vulvar carcinoma patients.

Tumor heparanase expression in predicting response to induction chemotherapy in patients with locally advanced laryngeal cancer.

PURPOSE: Induction chemotherapy is a feasible alternative to surgery for the treatment of locally advanced laryngeal cancer. Determining predictive factors associated with a better response to chemotherapy would help choose the patients most likely to benefit from larynx preservation. METHODS: Eighty-four patients diagnosed with locally advanced laryngeal cancer (stage III-IV) between April 1999 and May 2006 were retrospectively reviewed. Eightytwo of them received 2 cycles and 2 received only 1 cycle of cisplatin and 5-fluorouracil (5-FU) chemotherapy. Patients were then grouped, based on response to treatment, as either having complete response (CR), partial response (PR), stable (SD) or progressive disease (PD). Factors predicting response to treatment were evaluated. Paraffin blocks were immunohistochemically examined for heparanase activity to see for any link between heparanase expression and response to treatment. RESULTS: There were 73 males and 11 females with a mean age of 59 years. After induction chemotherapy (cisplatin and 5-FU), 33 patients achieved PR and 20 CR. SD and PD occurred in 9 and 21 patients, respectively. Patients with stage III disease had better overall (CR and PR) response rates when compared with those with stage IV disease. Moreover, development of bone marrow suppression and heparanase positivity were both associated with better overall response rates. CONCLUSION: This study supports the hypothesis that heparanase positivity is associated with better responses to induction chemotherapy, regardless of TNM stage. Furthermore, a higher overall response rate was observed in patients who developed myelosuppression secondary to chemotherapy.

Dosimetric comparison of robotic and conventional linac-based stereotactic lung irradiation in early-stage lung cancer.

We aimed to compare dosimetric characteristics of conventional linear accerator-based treatment plans to those created using the robotic CyberKnife® (CK) treatment planning system for patients with early-stage lung cancer. Eight early-stage lung cancer patients treated with stereotactic body radiotherapy (SBRT) using a conventional linac-based (LIN) system were included in this study. New treatment plans were created for the patients with the CK treatment planning system in order to compare the two platforms' dosimetric characteristics. Planning computed tomographies (CT) were obtained in three phases: free-breathing, full exhalation and inhalation. The three GTVs were then added together for internal target volume (ITV) with LIN, whereas no ITV was used for CK. Planning target volumes (PTV) were constituted by adding 5-mm margin to GTV and ITV. Treatment plan was 54 Gy in three fractions. Five-field, seven-field, and dynamic-conformal arc planning techniques were used in LIN plans. Plans were compared according to dose heterogenity (D(max)-maximum dose), volume of 54 Gy (V54) and 27 Gy isodose (V27), conformity index (CI(54) and CI(27)) and lung volumes. PTVs were significantly smaller in CK plans (p=0.012). D(max) was significantly lower in ARC plans (p=0.01). Among all plans, CK had significantly tightest isodose shell received 54 Gy and 27 Gy (p=0.0001). Among LIN plans, V54 was significantly (p=0.03) smaller in ARC plans; but no difference was observed for V27 values. LIN plans have better plan quality (CI(27) and CI(54)) than CK. No statistically significant difference was observed for lung volumes. CK plans had superior V54 and V27 values compared to LIN plans due to smaller PTV. LIN plans had better CI(27) and CI(54) values. Advantages of LIN treatment were no neccessity for fiducial marker use, which may cause pneumothorax, and significantly shorter beam-on treatment times. Both CK and LIN methods are suitable for lung SBRT.

Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study.

BACKGROUND: this study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. PATIENTS AND METHODS: data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. RESULTS: sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. CONCLUSIONS: combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.

Vaginal high dose rate brachytherapy alone in patients with intermediate- to high-risk stage I endometrial carcinoma after radical surgery.

The objective of this study was to analyze the efficacy and morbidity of vaginal cuff brachytherapy alone in intermediate- to high-risk stage I endometrial cancer patients after complete surgical staging. Between October 1994 and November 2005, 128 patients with intermediate- to high-risk stage I endometrial adenocarcinoma were treated with high dose rate (HDR) brachytherapy alone after complete surgical staging. The intermediate- to high-risk group was defined as any stage I with grade 3 histology or stage IB grade 2 or any stage IC disease. The comprehensive surgery was in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy in addition to infracolic omentectomy, and routine pelvic and para-aortic lymphadenectomy. The median number of the lymph nodes dissected was 33. The median age at the time of diagnosis was 60 years. Forty patients were staged as IB (grade 2: 25 and grade 3: 15), and 88 patients were staged as IC (grade 1: 31, grade 2: 41, and grade 3: 16). A total dose of 27.5 Gy with HDR brachytherapy, prescribed at 0.5 cm, was delivered in five fractions in 5 consecutive days. Median follow-up was 48 months. Six (4.7%) patients developed either local recurrence (n = 2) or distant metastases (n = 4). Five-year overall survival and disease-free survival (DFS) rates are 96% and 93%, respectively. Only age was found to be significant prognostic factor for DFS. Patients younger than 60 years have significantly higher DFS (P = 0.006). None of the patients experienced grade 3/4 complications due to the vaginal HDR brachytherapy. Vaginal cuff brachytherapy alone is an adequate treatment modality in stage I endometrial adenocarcinoma patients with intermediate- to high-risk features after complete surgical staging with low complication rates.

Radiotherapy in congenital vulvar lymphangioma circumscriptum.

Congenital lymphangioma circumscriptum (LC) of the vulva is a rare disorder with unknown etiology. Treatment options include ablative approaches such as laser therapy, sclerotherapy, and surgery. Radiotherapy has been shown to be effective in the management of congenital lymphangioma especially in the thoracic and abdominal lesions. In this report, we describe a patient with persistent vulvar LC despite sclerosing therapy and several surgical excisions. She was treated with a course of external radiotherapy and showed a dramatic objective response with relief of all symptoms.

Use of plasma Epstein-Barr virus DNA monitoring as a tumor marker in follow-up of patients with nasopharyngeal carcinoma: preliminary results and report of two cases.

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77-13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.

Long-term outcome and prognostic factors in patients with cervical carcinoma: a retrospective study.

This study evaluates treatment outcomes and possible prognostic factors of inoperable cervical cancer patients treated with external beam radiotherapy (EBRT) and high-dose rate brachytherapy (HDR BRT). Between 1993 and 2000, 183 patients with cervical cancer were treated at our institute. Radiotherapy was the sole treatment modality until January 1997; after the announcement of National Cancer Institute in 1999, 40 mg/m(2) of cisplatin (49%) was routinely applied every week. Median age was 54 years (32-92 years). Most patients (88%) had advanced-stage disease (IIB-IIIB). With a median follow-up time of 45 months (6-121 months), the 5-year overall survival (OS), local recurrence-free survival, disease-free survival (DFS), and distant metastasis-free survival (DMFS) rates were 55%, 71%, 51%, and 77%, respectively. Univariate analysis revealed that age, tumor size, lymph node status, and concomitant cisplatin were prognostic factors for OS. The DFS rates were lower in young age group. Patients with tumor greater than 4 cm and age greater than 40 were at greater risk for local recurrence. Distant metastases were more frequent in patients with adenocarcinoma. Concurrent cisplatin use increases DMFS rates (91% vs 78%; P= 0.05). In multivariate analysis, extensive stage, parametrial infiltration, young age, adenocarcinoma histopathology, and lymph node metastasis were negative prognostic factors for OS while concomitant cisplatin increases OS. Likewise, patients with extensive stage, adenocarcinoma, and without concurrent cisplatin administration had more risk for distant metastasis. There was no treatment-related mortality. Grade 3-4 morbidity rates were seen only in eight patients (4%). The combination of EBRT and HDR BRT together with concomitant chemotherapy in the treatment of locally advanced carcinoma of cervix is safe and well tolerated with acceptable morbidity.

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors.

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.

Frequency of skeletal metastases in nasopharyngeal carcinoma after initiation of therapy: should bone scans be used for follow-up?

Previous reports have indicated a relatively high incidence of distant metastases in patients with nasopharyngeal carcinoma (NPC), one of the most common sites being the skeleton. Although bone scintigraphy offers the advantage of whole-body imaging in patients with cancer by providing useful information about disease spread, its value in patients with NPC is not well defined because of cost-effectiveness considerations. In this study, we assessed the value of follow-up bone scintigraphy for the evaluation of skeletal metastases in patients with different stages of NPC. Between 1994 and 2001, 230 patients with histologically proven NPC were admitted to the Department of Radiation Oncology. Out of 230 patients, 171 were examined for skeletal metastases with bone scintigraphy prior to therapy and at 1 year intervals. Bone scintigraphy detected increased uptake in 29 patients, which was reported as suggestive of metastases or equivocal. Twenty-six of these were true-positive, confirmed by radiography or clinical follow-up. Bone pain was present in 67% of these patients and serum lactate dehydrogenase and alkaline phosphatase were elevated in 35% and 37%, respectively. The incidence of bone metastases correlated with the extent of lymph node involvement, which were detected after a median time of 10.5 months following the diagnosis of the primary disease. No correlation was observed between the metastatic status and local T stage, histological differentiation age or gender of the patient. We can therefore recommend that bone scintigraphy be used in determining the presence of bone metastases, but its utilization should be preserved for those with nodal involvement.

Outcome of abducens nerve paralysis in patients with nasopharyngeal carcinoma.

PURPOSE: The objective of this study was to investigate the incidence, management and outcome of patients with nasopharyngeal carcinoma (NPC) who developed Vlth nerve palsy. METHODS: Between December 1993 and December 1999, we investigated retrospectively the charts of 166 patients with NPC. RESULTS: Twenty-eight of 166 patients (16.8%) had cranial nerve involvement at the time of the diagnosis of NPC. Sixteen (57.2%) were identified as having abducens nerve palsy. In 25% abducens nerve palsy was the presenting symptom. Three patients were able to compensate for their diplopia after prism correction or botulinum toxin-A injection, and six (50%) completely recovered from abducens nerve palsy after either radiotherapy or chemotherapy. CONCLUSIONS: Abducens is the most common cranial nerve involved in NPC, radiotherapy and or chemotherapy relieves the paralysis in half the patients. Prism correction or botulinum toxin-A injection are effective non-invasive procedures for patients with significant diplopia.

Radiotherapy in the management of Kasabach-Merritt syndrome: a case report.

A 21-day-old infant with hemangioma was brought to the hospital with enlargement of the hemangioma of the left thigh and purple discoloration around umbilicus. This led to the diagnosis of Kasabach-Merrill syndrome. Initial treatment with corticosteroid failed. The patient underwent radiotherapy that led successfully to improvement of both hemangioma and thrombocytopenia. After 2 years of follow-up, the patient has experienced long-term complications, including atrophy and growth retardation of the irradiated leg.

Malignancy in Behçet's disease: a report of 13 cases and a review of the literature.

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.