Local Low-dose Anti-PD-L1 Antibodies Improve Antitumor Effects in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors are highly effective for treating recurrent and metastatic head and neck cancers. However, they require systemic administration and are associated with immune-related adverse events (irAEs). Reducing therapeutic antibody doses to prevent irAEs is challenging. MATERIALS AND METHODS: Mouse buccal mucosa squamous cell carcinoma cells (Sq-1979) were transplanted into the backs of mice to induce tumors. The antitumor efficacy and tumor immunohistological environment in tumor-bearing mice were compared after administering a standard dose of programmed death-ligand 1 (PD-L1) antibodies systemically (200 mg/body) or 1/10th of the standard dose (20 mg/body) directly to tumors. Mice received four doses of antibody administered in 3-day intervals. Tumor reduction rates and antitumor efficacies were evaluated 21 days after initiating treatment. CD8+T cell counts and PD-L1, PD-1, perforin, and granzyme B levels; CD25 and Foxp3 expression levels; and tumor Tregs were assessed in the resected subcutaneous tumors. RESULTS: The antitumor efficacies in the local low-dose and systemic standard-dose groups were compared with that of the control group. The efficacies of the two treatment groups were similar, and both treatment groups revealed significant antitumor effects compared to the control group. Perforin and granzyme B levels were higher in the local low-dose group (p<0.05). CONCLUSION: Local low-dose administration of anti-PD-L1 antibodies exhibits antitumor efficacy similar to systemic standard-dose administration suggesting that local low-dose administration is useful for treating oral squamous cell carcinoma.

The ECAS system can superselectively administer anticancer drugs to numerous feeding arteries from the superficial temporal artery: A case report and literature review.

Superselective intra-arterial chemoradiotherapy (SSIACRT) is one of the curative treatments for advanced oral cancer. SSIACRT can reportedly treat cervical lymph node metastases in the level I-IIA area by super selectively catheterizing the facial artery (FA) and infusing drugs. However, since advanced oral cancer lesions involve a number of feeding vessels, retrograde treatment requires the placement of catheters from the superficial temporal artery (STA) and occipital artery (OA). Furthermore, in the case of level IIB lymph node metastasis, the catheter must be changed because it is necessary to administer anticancer drugs to more than three routes, including the OA, when the feeding arteries of the primary tumor are combined. The external carotid artery sheath (ECAS) system used in the present study involves the insertion of a microcatheter or steering catheter from one route of the STA, allowing selection of numerous feeding vessels, including the OA. The ECAS system can facilitate the administration of chemotherapy via the STA simultaneously to the maxillary artery, lingual artery, FA and OA. The present study describes cases of maxillary gingival cancer and tongue cancer with cervical lymph node metastasis, which were treated with the ECAS system via the STA; the treatment successfully controlled both the primary tumor and cervical lymph node metastasis. In the two cases described in the present study, metastatic lymph nodes were found in the level ⅠB and ⅡB region, but were successfully treated by administering cisplatin via the OA, in addition to the primary lesion. To date, to the best of our knowledge, there is no case report clearly referring to the treatment of lymph node metastasis using the ECAS system. In conclusion, SSIACRT using ECAS may be considered a useful treatment for oral cancer with cervical lymph node metastasis.

Endoscopic Laryngopharyngeal Surgery Combined with Endoscopic Submucosal Dissection as a Treatment Option for Superficial Hypopharyngeal Cancer with Suspected Synchronous Lymph Node Metastasis.

We report 4 cases of hypopharyngeal cancer preoperatively suspected with synchronous lymph node metastases. Pathologic lymph node metastasis was confirmed in three of the four cases. All 4 cases underwent endoscopic laryngopharyngeal surgery (ELPS) combined with endoscopic submucosal dissection (ESD) and subsequent lymph node dissection as an optional treatment rather than the standard treatment. Peroral resection for primary site was selected because of the expected decline in quality of life (QoL) after radical surgery. Among 4 patients, one developed local recurrence; however, the other three remained recurrence-free and survived without any additional treatment. Furthermore, the patient who developed local recurrence had a recurrence-free survival for more than 5 years, with additional chemoradiation therapy. No disorders in speech, swallowing, or breathing was observed during the follow-up period. ELPS combined with ESD is generally indicated for laryngopharyngeal cancer without synchronous lymph node metastasis. However, this can be a treatment option for patients may wish to preserve a greater QoL after treatment. In the future, when more data on the results and long-term prognosis of this treatment are accumulated, it may be possible to discuss its validity further.

Initial Experience of Intra-Arterial Chemotherapy Using a Novel External Carotid Arterial Sheath System Combined with Radiotherapy and Systemic Chemotherapy for Locally Advanced Tongue Cancer.

We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III-IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer.

Intratumor hemodynamics using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancer.

OBJECTIVE: The objectives of the study were to estimate the perfusion of tumors by drugs used in intra-arterial chemotherapy for head and neck cancer with magnetic resonance imaging and to establish the factors involved in determining the optimal dose. STUDY DESIGN: Contrast agent was administered intra-arterially into either the lingual or maxillary artery in 43 patients. Triple-phase continuous fast spin echo magnetic resonance imaging was performed. Changes in blood water longitudinal relaxation rate (⊿R1) were measured in relation to imaging phase, type of artery, measurement site, and tumor size. RESULTS: ⊿R1 was significantly higher at the tumor margin than at the center for both arteries, except in the first phase for the lingual artery. ⊿R1 was greatest in the third phase for the lingual artery and in the second phase for the maxillary artery. For both arteries, as the tumor size increased, there was a significant decrease in ⊿R1 at the center of the tumor compared with the margin. CONCLUSIONS: The factors associated with ⊿R1 were imaging phase, type of artery, measurement site, and tumor size. When determining a drug's optimal dose, the type of artery and tumor size must be taken into consideration.

General rules for clinical and pathological studies on oral cancer (2nd edition): a synopsis.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the "Rules" section is primarily presented.

Verification of the junctional dose for irradiation of the chest wall and supraclavicular regions under the circumstances of advanced technologies.

A single-isocenter half-beam technique is commonly used when irradiating the chest wall and supraclavicular regions in patients with high-risk breast cancer. However, several studies have reported that underdosage can occur at the junction of the chest wall and supraclavicular regions due to a "tongue-and-groove" effect. This study verified the efficacy of an open leaf technique (OL-tech) that involves placing a multileaf collimator 5 mm outside from the beam central axis to remove the effect of the multileaf collimator in a single-isocenter half-beam technique. We compared the junction doses of the OL-tech with those of a conventional technique (C-tech) in square and clinical plans, using 4 and 10 MV x-rays in the Clinac iX and 6 and 10 MV x-rays in the Trilogy accelerators (Varian Medical Systems, Palo Alto, CA). EBT3 radiochromic films were used for measurements. Measurements were performed at a depth of 3 cm when verifying field matching. The EBT3 films in the square plan indicated junction doses for the C-tech of 78.3% with the Clinac iX accelerator and 73.6% with the Trilogy accelerator. By contrast, the corresponding doses for the OL-tech were 107.2% and 99.8%, respectively. In the clinical plan, the junction doses for the C-tech were 76.5% with the Clinac iX accelerator and 72.6% with the Trilogy accelerator; the corresponding doses for the OL-tech were 108.3% and 101.7%, respectively. As with the square plan, variations in the junction dose were much smaller using the OL-tech than using the C-tech. Our results suggest that the OL-tech can be useful for improving dose homogeneity at the junction of the chest wall and supraclavicular regions.

Efficacy of polyglycolic acid sheets and fibrin glue for the prevention of post-ELPS bleeding.

OBJECTIVE: To assess the efficacy and safety of a covering method using polyglycolic acid (PGA) sheets and fibrin glue in preventing laryngopharyngeal bleeding after endoscopic laryngopharyngeal surgery (ELPS) combined with endoscopic submucosal dissection (ESD). METHODS: Twenty-one patients who underwent ELPS combined with ESD (28 resected pharyngeal carcinomas) were retrospectively evaluated. After completing ELPS combined with ESD, fibrinogen was sprayed onto the ulcer. A PGA sheet cut into 5 × 5 mm pieces that fit the size of the ELPS-induced ulcer was then placed over the ulcer and fixed in place with a fibrin glue comprising thrombin. RESULTS: The resection procedure was performed for all lesions. The median long diameter of the resected specimen was 36 mm. The rate of a resected specimen diameter >30 mm, use of anticoagulant/platelet, and macroscopic classification 0-Ⅱa were 68% (19/28), 19% (5/28), and 36% (10/28), respectively. The median time required to cover ELPS-induced ulcers using PGA sheets and fibrin glue was 10 min (range: 3-22 min). No post-ELPS bleeding, subcutaneous emphysema, or aspiration pneumonia (0/28) was observed. CONCLUSION: The covering method using PGA sheets and fibrin glue for ELPS-induced ulcers is considered to be sufficiently safe and effective in preventing post-ELPS laryngopharyngeal bleeding. This method could be useful in preventing post-ELPS bleeding in patients with head and neck cancer.

Proton Therapy for Localized Prostate Cancer: Long-Term Results From a Single-Center Experience.

PURPOSE: Although proton therapy is controversial, it has been used to treat localized prostate cancer over the past 2 decades. The purpose of this study is to examine the long-term efficacy and toxicity of proton therapy for localized prostate cancer. METHODS AND MATERIALS: This was a retrospective observational study of 2021 patients from 2003 to 2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and 6% of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated using the Kaplan-Meier method and were analyzed using multivariable Cox proportional hazards models. RESULTS: The median follow-up period was 84 months (interquartile range, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100% and 100%, 99% and 88%, 93% and 86%, 90% and 79%, 88% and 68%, and 76% and 63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high-risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. The results of multivariable analyses indicate that younger patients more often experienced biochemical relapse. CONCLUSIONS: This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that accounts for the patient's age.

Drug concentration estimation using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancers.

OBJECTIVE: In cases of head and neck cancer treated with intra-arterial chemotherapy, no objective indices are available for determining the distribution of anticancer drugs administered to multiple arteries. To establish such indices, noninvasive measurements of drug concentrations are required in the arterial perfusion area of each artery. In MRI, changes in 1/T1 (Δ1/T1) are correlated with the contrast agent concentration. We focused on these properties and investigated whether it is possible to estimate anticancer drug concentrations within tissue based on Δ1/T1. METHODS: We employed the fast spin echo (FSE) sequence to determine optimum imaging parameters using a phantom. Subsequently, contrast agent was administered via the lingual and external carotid arteries for seven cases of tongue cancer. Δ1/T1 were then measured in tumor and nontumor tissues. The results of this study were compared with those of a previous study in which intratumor concentrations of anticancer agent were measured in excised specimens. RESULTS: The optimum imaging parameters for the FSE was two repetition times (TR, 500 and 1000 ms). When compared with the external carotid artery administration, the lingual artery administration of contrast agent resulted in significantly higher Δ1/T1 in both tumor and nontumor tissues (2.13 and 2.62 times, respectively). The multiplying factor for the nontumor tissue and high homogeneity of the contrast agent concentration were reasonably consistent with the results of the previous study. CONCLUSION: This method can be applied to estimating intratissue concentrations of intra-arterially administered anticancer drugs, thus possibly providing useful information in determining the distribution of anticancer drugs.

Dose-Volume Comparison of IMRT and PSPT Treatment Plans for Early-Stage Glottic Cancer.

PURPOSE: To clarify the dose distribution characteristics for early-stage glottic cancer by comparing the dose distribution between intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) and to examine the usefulness of PSPT for early-stage glottic cancer. MATERIALS AND METHODS: Computed tomography datasets of 8 patients with T1-2 glottic cancer who had been treated by PSPT were used to create an IMRT plan in Eclipse with 7 fields and a PSPT plan in XiO-M with 2 fields. Organs at risk (OARs) included the carotid arteries, arytenoids, inferior constrictor muscles, strap muscles, thyroid cartilage, cricoid cartilage, and spinal cord. The prescription dose was 66 GyRBE in 33 fractions to the planning target volume (PTV). All plans were optimized such that 95% of the PTV received 90% of the prescription dose considering that the skin was slightly spared. RESULTS: The superiority of the PSPT was confirmed in all OARs. In the PSPT, the dose to the contralateral carotid artery and the spinal cord, which is slightly distant from the PTV, was dramatically reduced while maintaining the dose distribution uniformity of the PTV by comparison with IMRT. CONCLUSION: PSPT for early-stage glottic cancer resulted in good target dose homogeneity and significantly spared the OARs as compared with the IMRT. PSPT is expected to be effective in reducing late effects and particularly useful for young people.

Stability of daily rectal movement and effectiveness of replanning protocols for sparing rectal doses based on the daily CT images during proton treatment for prostate cancer.

PURPOSE: To evaluate the optimal period of replanning to spare the rectal dose by investigating daily rectal movements during computed tomography (CT) image-guided proton therapy for prostate cancer. MATERIALS AND METHODS: To evaluate the optimum reference period for replanning, we analyzed 1483 sets of daily CT (dCT) images acquired from 40 prostate cancer patients and measured the daily rectal movement along the anterior-posterior direction based on the simulator CT (sCT) images and dCT images. We calculated daily dose distributions based on initial plans on the sCT images and replans on the dCT images for 13 representative patients, and evaluated daily dose volume histograms (DVHs) for the prostate, seminal vesicles, and rectum. RESULTS: The rectal anterior side on the dCT images around the seminal vesicles largely deviated toward the anterior side relative to the position on the reference sCT images, but the deviation decreased by referring to the dCT images and became nearly zero when we referred to the dCT images after 10-day treatment. The daily DVH values for the prostate showed good dose coverage. For six patients showing rectal movement toward the anterior side, the daily rectal DVH (V77% ) showed a 3.0 ± 1.7 cc excess from the initial plan and this excess was correlated with 9.9 ± 6.8 mm rectal movement. To identify the patients (37.5% in total) for whom the replanning on the 10th-day and 20th-day CT images reduced the V77% excess to 0.4 ± 1.5 cc and -0.2 ± 1.3 cc, respectively, we evaluated the accumulated mean doses with a 1.2 cc criterion. CONCLUSION: Our data demonstrate that the daily movement of the rectal anterior side tends to move toward the anterior side, which results in a rectal overdose, and the mean of the movement gradually decreases with the passage of days. In such cases, replanning with the reference CT after 10 days is effective to spare the rectal dose.

Proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for an extremely rapid growing recurrent ameloblastic carcinoma: A case report.

Ameloblastic carcinoma (AC) is a very rare malignant odontogenic tumor. Although surgical resection is generally performed, treatment approaches have not been established for recurrent cases. Chemotherapy and radiotherapy are positioned as adjunctive therapies, and few studies investigated definitive non-operative therapy. We present the case of a 71-year-old male with recurrent secondary-type AC arising from the right maxilla, who was treated with proton beam therapy (PBT; 71.4 Gy relative biological effectiveness in 32 fractions) combined with continuous intra-arterial infusion of cisplatin (40 mg/m2) and docetaxel (8 mg/m2). The patient experienced acute grade 3 mucositis, dermatitis and neutropenia, which were resolved within 3 months of treatment. Late adverse events were grade 1 skin atrophy, and grade 2 right optic nerve disorder and retinopathy. After ~8 years of treatment, the patient died from another cause but did not experience any relapse or metastasis during the follow-up period of 94 months. To the best of our knowledge, this is the first report of recurrent AC treated with PBT and intra-arterial infusion chemotherapy without any severe late adverse events. This combination therapy approach may be considered as an effective therapeutic option for inoperable AC.

Proton Beam Therapy for Locally Recurrent Parotid Gland Cancer.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5-8 weeks). The median follow-up was 24 months (range 10-49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3-5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

Proton Beam Therapy Combined with Intra-Arterial Infusion Chemotherapy for Stage IV Adenoid Cystic Carcinoma of the Base of the Tongue.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15-116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Treatment outcomes of proton or carbon ion therapy for skull base chordoma: a retrospective study.

BACKGROUND: The usefulness of particle therapy for skull base chordoma has not been established. The aim of this retrospective study was to analyse the treatment outcomes of proton therapy (PT) and carbon ion therapy (CIT) in patients with skull base chordoma at a single institution. METHODS: All patients who underwent PT or CIT with curative intent between 2003 and 2014 at Hyogo Ion Beam Medical Center were included in this study. Twenty-four patients were enrolled. Eleven (46%) received PT and 13 (54%) received CIT. Overall survival (OS), progression-free survival (PFS) and local control (LC) were calculated using the Kaplan-Meier method. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up was 71.5 months (range, 14-175 months). The five-year LC, PFS and OS rates were 85, 81, and 86%, respectively. The LC (P = 0.048), PFS (P = 0.028) and OS (P = 0.012) were significantly improved in patients who had undergone surgery before particle therapy. No significant differences were observed in the LC rate and the incidence of grade 2 or higher late toxicities between patients who received PT and CIT. CONCLUSIONS: Both PT and CIT appear to be effective and safe treatments and show potential to become the standard treatments for skull base chordoma. To increase the local control, surgery before particle therapy is preferable.

A comparison of two types of microcatheters used for a novel external carotid arterial sheath system for intra-arterial chemotherapy of head and neck cancer.

PURPOSE: We developed an external carotid arterial sheath (ECAS) for performing intra-arterial chemotherapy (IACT) via the superficial temporal artery for head and neck cancer. This study aimed to assess the potential of a novel microcatheter with a steerable tip inserted through the ECAS in comparison to an existing hook-type microcatheter. MATERIALS AND METHODS: The same operator used two types of microcatheters alternately for each weekly IACT session with the same patient, and the fluoroscopy time required for catheterization and the arterial selectivity of each microcatheter were compared. RESULTS: Ten patients with advanced head and neck cancer were enrolled. The steerable microcatheter significantly shortened the fluoroscopy time required for catheterization in comparison to the hook-type microcatheter (45.9 ± 4.8 vs 70.2 ± 9.8 s, p < 0.02). The arterial selectivity was equivalent [97.1%, (34/35) vs 88.6%, (31/35), p = 0.36]. No serious adverse events were observed in association with the procedure. CONCLUSION: In combination with an ECAS, the steerable microcatheter might be more useful than the hook-type microcatheter.

Outcomes of Patients With Sinonasal Squamous Cell Carcinoma Treated With Particle Therapy Using Protons or Carbon Ions.

PURPOSE: This retrospective study aimed to determine the clinical outcomes following particle monotherapy (ie, proton therapy [PT] or carbon ion therapy [CIT]) in patients with sinonasal squamous cell carcinoma at a single institution. METHODS AND MATERIALS: Between August 2001 and March 2012, 59 patients were treated with definitive PT or CIT; none underwent chemotherapy or surgery. Of the patients, 22 (37%) had unresectable disease. PT was used in 38 patients (64%); CIT, 21 patients (36%). Almost half of the patients (n = 29, 47%) received 65.0 Gy (relative biological effectiveness) in 26 fractions. RESULTS: The median follow-up period was 30 months (range, 8-127 months) for all patients and 65 months (range, 9-127 months) for the survivors. The 3- and 5-year overall survival rates were 56.2% and 41.6%, respectively; progression-free survival rates, 42.9% and 34.7%, respectively; and local control rates, 54.0% and 50.4%, respectively. Late toxicities of grade ≥3 occurred in 13 patients (22%). CONCLUSIONS: To our knowledge, this is the largest retrospective study of sinonasal squamous cell carcinoma treated with particle therapy alone. The efficacy of PT and CIT indicated that particle therapy can serve an important role in treating this disease.

Pathology and images of radiation-induced hepatitis: a review article.

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PURPOSE: We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. MATERIALS/METHODS: We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. RESULTS: The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. CONCLUSION: The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment.