Prostate specific antigen bounce after intensity-modulated radiation therapy in an Asian population

Objective:Serum prostate specific antigen(PSA)is commonly used to evaluate treatment response after definitive radiation therapy(RT).However,PSA levels can temporarily rise without a clear reason,termed“PSA bounce”,and often engender great anxiety for both patients and physicians.The present study aimed to determine the prevalence and factors that predict“PSA bounce”after intensity-modulated radiation therapy(IMRT),and the relevance to biochemical failure and cancer recurrence in an Asian population.Methods:We retrospectively reviewed 206 patients who received IMRT for prostate cancer from 2004 to 2012 in the National Cancer Centre Singapore.These patients were followed up with regular PSA monitoring.We defined“PSA bounce”as a rise of 0.1 ng/mL,followed by two consecutive falls.Patients with biochemical failure(PSA nadir t 2 ng/mL)were further evaluated for cancer recurrence.Results:Sixty-one patients(29.6%)experienced“PSA bounce”,at a median time of 16 months and lasted for 12 months.Age remained the most consistent predictor of the incidence,duration and extent of“PSA bounce”.Other contributory factors included baseline PSA,Gleason score and PSA nadir.Hormonal therapy and prostate volume did not affect this phenomenon.Sixteen patients(7.8%)developed biochemical recurrence,at median time of 32 months,of which 11 were confirmed to have metastatic disease.The median follow-up time was 71 months.

Clinical study on concurrent and sequential therapy of intensity modulated radiation therapy (IMRT) combined with NP regimen chemotherapy in the treatment of middle and advanced non-small cell lung cancer

Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin (NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; (4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall re- sponse, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.

Intensity Modulated Proton Therapy for Re-Irradiation of Bulky Loco-Regional Recurrent Breast Cancer: A Case Report

Patients with recurrent breast cancer to chest wall, who had previous irradiation, are difficult to manage and have limited options. Several reports described the use of photon therapy, hyperthermia, and brachytherapy. This is a case report of a 72-year-old female with Stage IIIA (pT3N1M0) invasive ductal carcinoma of the right breast status post modified radical mastectomy. The patient developed recurrence to the chest wall and one internal mammary lymph node one year later. She received 3-D conformal photon radiation therapy for this recurrence. Two years later, she had progression of the recurrence at the right chest wall and axillary and internal mammary lymph nodes. She was treated with intensity modulated proton therapy (IMPT) for a total of 6600 cGy in 33 fractions. However, four months later, she was found to have biopsy-proven isolated metastatic disease at her right bicep, which was again treated with IMPT for a dose of 6000 cGy in 20 fractions. Proton beam therapy was used in this case to spare dose to the brachial plexus, heart and lung while optimally irradiating the recurrent tumors. At last follow up, the patient is alive and has been disease free for 39 months. This report describes the technique and dosimetry for this unique case, which also reviewed recent series of re-irradiation using proton beam.

Helical tomotherapy and volumetric modulated arc therapy:New therapeutic arms in the breast cancer radiotherapy

AIM To analyse clinical and dosimetric results of helical tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in complex adjuvant breast and nodes irradiation.METHODS Seventy-three patients were included(31 HT and 42 VMAT). Dose were 63.8 Gy(HT) and 63.2 Gy(VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes(SCN) and internal mammary chain(IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort(7 mm vs 5 mm).RESULTS For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC:96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5%(HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2%(VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1%(HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9%(VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy(HT) and 4.6 ± 0.9 Gy(VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts.CONCLUSION HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Role of radiation therapy in gastric adenocarcinoma

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

Complete response to radiation therapy of orbital metastasis from hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC)is increasing in the United States,and 50%-75%o patients with HCC will develop metastatic disease Orbital metastases from HCC are extremely rare.We report the case of a 52-year-old male with known metastatic HCC,who presented with severe proptosis and diplopia.An orbital mass was identified on magnetic resonance imaging(MRI)and confirmed to have hypermetabolic activity on positron emission tomography/computed tomography.He received a palliative course of external beam radiation therapy to the right orbit.Intensity modulated radiation therapy (IMRT)was used to allow sparing of critical norma tissues in close proximity to the tumor.One month after completion of IMRT to 58 Gray in 30 fractions delivered over 6 wk,the patient had a complete clinical,radiologic(MRI)and symptomatic response The patient continues to have local control in the orbi 1.7 years after therapy completion.All critical norma structures were kept below the tolerance dose using IMRT,and no toxicities were observed.

Treatment of Massive Low-Grade Chondrosarcoma of Nasal Septum with Helical Tomotherapy: A Case Report

Chondrosarcomas are malignant bone tumors which develop as a cartilaginous differentiation of primary mesenchymal cells and the second most frequently seen malignant tumor of the bone after osteosarcoma. These malignancies are slowly growing non-epithelial tumors with unknown etiology and most frequently seen during the 4 decades of life. They are frequently localized on pelvis, ribs and long bones. Nasal septum CSs are very rarely seen malignancies. They originate from septal mucosa or cartilage and it is difficult to make a diagnosis unless they reach a certain size. A few cases of CSs with nasal septum have been reported in the literature. In cases of CSs, surgery is the gold standard treatment modality;however in surgically unresectable cases or close to margins, radiotherapy plays a significant role in primary and adjuvant treatment. Based on the position of the tumor in head and neck and extremely closeness of the tumor to vital organs as optic nerve, chiasm and brain, image guided-intensity modulated radiation therapy (IG-IMRT) becomes very effective and reliable modalities and may be a favorable treatment alternative.

Neoadjuvant chemoradiotherapy for locally advanced gastric cancer with bulky lymph node metastasis:Five case reports

BACKGROUND Neoadjuvant chemoradiotherapy(NACRT)has not been accepted as a general therapy for gastric cancer because of its localized effect and toxicity for radiosensitive organs.However,if radiation therapy could compensate for the limited or inadequate treatment choices available for elderly patients and/or those at high risk,the available therapeutic options for advanced gastric cancer might increase.From this perspective,we present our experiences of five patients with advanced gastric cancer in whom we used NACRT therapy with interesting results.CASE SUMMARY We admitted five patients with clinical Stage III gastric cancer and bulky lymph node metastasis or adjacent organ invasion at the time of diagnosis.A total of 50 Gy of preoperative intensity modulated radiation therapy was delivered to the patients in doses of 2.0 Gy/d,together with a regimen of concomitant chemotherapy comprising two courses of oral tegafur/gimeracil/oteracil(S-1;65 mg/m2 per day)for three consecutive weeks followed by two weeks of rest,starting at the same time as radiotherapy.All patients underwent no residual tumor resection and a pathological complete response of the primary tumors was achieved in two patients.The incidence of hematological toxicity was low,although the digestive toxicities of anorexia and diarrhea developed in three of the five patients,necessitating termination of radiation therapy at 30 Gy and S-1 at three weeks.However,even 30 Gy of irradiation and half the dose of S-1 resulted in sufficient downstaging,indicating that even a reduced amount of NACRT could confer considerable effects.CONCLUSION Slightly reduced NACRT might be useful and safe for patients with locally advanced gastric cancer.

Proton beam therapy of periorbital sinonasal squamous cell carcinoma: Two case reports and review of literature

BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common histology,with poorer prognosis.In the setting of orbital invasion,an orbital exenteration may be required.However,in case of primary rejection of disfiguring surgery or unresectable disease,proton beam therapy(PBT)should be largely considered,allowing for better sparing of neighboring critical structures and improved outcomes by dose escalation.CASE SUMMARY A 62-year-old male presented with a recurrent SCC in the nasal septum abutting frontal skull base and bilateral orbits at 7 mo after primary partial nasal amputation.Because of refusal of face-deforming surgery and considerable adverse effects of conventional radiotherapy,the patient underwent a PBT by hyperfractionated accelerated scheme,resulting in complete response and moderate toxicities.After 2 years,a nasal reconstruction was implemented with satisfactory appearance and recurrence-freedom to date.Another patient with an initially extended sinonasal SCC,invading right orbit and facial soft tissue,declined an orbital exenteration and was treated with a normofractionated PBT to the gross tumor and elective cervical lymphatics.The follow-up showed a continuous tumor remission with reasonable late toxicities,such as cataract and telangiectasia on the right.Despite T4a stage and disapproval of concurrent chemotherapy owing to individual choice,both patients still achieved outstanding treatment outcomes with PBT alone.CONCLUSION PBT enabled orbit preservation and excellent tumor control without severe adverse effects on both presented patients with locally advanced sinonasal SCC.

Dose Distribution Verifications of IMRT for NPC

In order to explore a dose distribution verification procedure of intensity modulated radiation therapy （IMRT） for nasopharyngeal carcinoma （NPC） and establish its evaluation criteria, we performed 35 two-dimensional （2D） patient-specific IMRT verifications over the year i006. The percent of pixels passing 7 and the normalized agreement test （NAT） index were mainly used to represent the agreement between the measured and computed dose distributions with three criteria （2%/2 mm, 3%/3 mm and 5%/3 mm） as recommended in the literature. The results were that all cases passed through verifications with three criteria except that the NAT index of one case was beyond the limitation, and the three tolerance levels of 2%/2mm, 3%/3 mm and 5%/3 mm produced similar clinical verification results but led to different percent of pixels passing Y and NAT index. Our data showed that the percent of pixels passing y and the NAT index were complementary to evaluate future IMRT verifications as two significant metrics. Due to the influence of the noise and the trait of the software, we considered an IMRT plan as acceptable in case of the percent ofpixels passing y 〉95% and the NAT index 〈5 with the 5%/3 mm criteria for IMRT patient-specific quality assurance （QA）.

A Systematic Approach to Patient-Specific Quality Assurance for Volumetric Modulated Arc Therapy

We developed the first non-commercial treatment planning system for volumetric modulated arc therapy(VMAT) in the United States. Because VMAT involves multi-parameter modulations, it is imperative to develop a comprehensive, rigorous and yet, practical procedure for routine patient-specific quality assurance(QA). In this paper, we presented our own approach as being currently implemented in our institution.Our patient-specific QA procedure involves multi-levels: pre-treatment QA,on-treatment QA, and posttreatment QA. The pre-treatment QA focuses on dosimetry verification, which is done with the commercial Map CHECK in Map PHAN mounted on an isocentric mounting fixture(IMF). This method is also referred to the fixed-gantry technique,i.e., the beams always remain perpendicular to the detector plane. The on-treatment QA involves in vivo optically stimulated luminescent dosimetry(OSLD).Prior to the treatment, two nano Dot TM OSLD dosimeters are placed on the patient abdomen under 1 cm bolus at the isocenter location. The irradiated dosimeters are then read by a nano Dot TM reader and the average reading of the two is calculated. The post-treatment QA involves the analysis of the Dyna Log and DLog files. The Dyna Log is a treatment log file that contains the planned and actual leaf positions at a given gantry angle. The DLog is a treatment log file that contains the planned segmented treatment table(STT) and the corresponding segment boundary samples, i.e., the actual delivered MU and gantry angle increment at each control point.

Research Progress of Two-d imensional Matrix Detectors in IMRT Dose Verification

With the continuous development of science and technolog ies in China,radiotherapy technology in medical field has been very significant ly developing,and intensity modulated radiation therapy(IMRT)technology has been the most widely used.This paper first introduces the components and types of two-dimensional matrix detector,two-dimensional ionization chamber matrix detector and two-dimensional semiconductor matrix detector,then analyzes the dosimetric characteristics of the two-dimensional matrix detector.In the end,the various applications of the two-dimensional matrix detector are analyzed and discussed in detail.The paper aims to promote the two-dimensional matrix detector’s development in the field of radiotherapy in China.

The role of radiotherapy in the treatment of oral cavity cancer

Radiotherapy plays a critical role in the treatment of oral cavity squamous cell carcinoma as monotherapy in early stage cancer or combined with surgery and/or chemotherapy in advances ones.Recent developments in the imaging of cancer and radiation technology have allowed developing more precise delivery of treatment with recent data demonstrating improvement in survival and lessening of adverse toxics effects of radiation.This review will focus in the recent advances and current state-of-the-art in radiation oncology both external beam radiotherapy and brachytherapy.As complexity of cancer treatments increases a close coordination between head-neck surgeons and radiation oncologist is needed due to a significant proportion of patients will be treated with combined modality therapy.

Adaptive Dose-Compensation Technique for Image-Guided Radiotherapy of Prostate Cancer

Background: For image-guided radiotherapy(IGRT) of prostate cancer, the current standard is online image guidance which can effectively correct setup errors and inter-fraction rigid organ motion. However, planning margins are still necessary for deformation and intra-fraction motion. Objective: This paper aims to investigate an adaptive planning technique incorporating offline dose feedback to manage interfraction motion and residuals from online corrections. Methods:Repeated CT scans from 28 patients were studied. Online IG was simulated by matching center-of-mass of prostate. A seven-beam IMRT plan with zero margins was designed for each patient. Dose distribution at each fraction was evaluated based on actual target and OARs from that fraction. Cumulative dose was calculated using deformable registration and compared to initial plan. If deviation exceeded pre-defined 2% threshold in prostate D99 an adaptive planning technique called dose compensation was invoked, in which cumulative dose was fed back to the planning system and dose deficit was made up through boost radiation in future fractions through IMRT. Results: If 2% under-dose was allowed at the end of course, then 11 patients failed. If the same criteria was assessed at the end of each week(every 5 fractions), then 14 patients failed. The average dose deficit for these 14 patients was4.4%. They improved to 2% after weekly compensation. 10(out of 14) patients passed criterion after weekly dose compensation; 3 failed marginally; 1 failed significantly(10% deficit). A more aggressive compensation frequency(every 3 fractions) could reduce the dose deficit to the acceptable level for this patient. The doses to OARs were not significantly different from online IG only without dose compensation.Conclusion: We demonstrated an offline dose compensation technique in prostate IGRT which can effectively account for residual uncertainties uncorrectable in online IG. Dose compensation allows further margin reduction and critical organs sparing.