Avoiding Dosimetric Risk Factors for Complications in Neoadjuvant Chemoradiotherapy for Lung Cancer: Conventional Radiotherapy Versus Intensity-modulated Radiotherapy.

BACKGROUND/AIM: We compared three-dimensional conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) for avoiding dosimetric risk factors related to pulmonary complications after neoadjuvant chemoradiotherapy followed by surgery (NACRT-S) for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We performed simulations in 11 patients with dosimetric risk factors during their treatment with NACRT-S for NSCLC. Radiation treatment plans were generated using 3D-CRT and IMRT to avoid dosimetric risk factors. Regarding dose-volume histogram (DVH) parameters, we calculated the percentage of lung volume that received more than x Gy (Vx) using 1) the total lung volume minus gross tumor volume (DVHg), 2) the lung volume remaining after surgery (DVHr), and 3) the contralateral lung volume (DVHc). We analyzed the dosimetric differences between 3D-CRT and IMRT. RESULTS: V35g and V40g were significantly lower with IMRT than with 3D-CRT (p=0.001 each); the median V35g and V40g were 16.1% and 14.9% with 3D-CRT versus 12.0% and 9.2% with IMRT, respectively. Overall, 0% and 55% of the patients were able to avoid all dosimetric risk factors with 3D-CRT and IMRT, respectively (p=0.006). Even with IMRT, tumor location and length of the planning target volume (PTV) significantly affected the avoidance of all dosimetric risk factors (p=0.015 and 0.022, respectively). CONCLUSION: IMRT is more useful than 3D-CRT for avoiding dosimetric risk factors in NACRT-S for NSCLC. For further improvements in avoiding these factors, respiratory motion managements to reduce the length of the PTV may be required for patients with middle or lower lobe tumors.

A Prospective Study of Intensity-modulated Radiation Therapy Using a Standard Radiation Dose for High-grade Glioma.

BACKGROUND/AIM: We evaluated the treatment outcomes of intensity-modulated radiation therapy (IMRT) using a standard radiation dose in patients with high-grade glioma (HGG). PATIENTS AND METHODS: We conducted a prospective, single-institutional, single-arm trial. Patients aged 20-75 years with histologically proven HGG were enrolled. Surgical procedures and chemotherapy regimens were not regulated. The prescribed dose of postoperative IMRT was 60 Gy in 30 fractions over six weeks. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), completion rate of IMRT, and Grade 3 or higher non-hematological toxicity. RESULTS: Between 2016 and 2019, 20 patients were enrolled. According to the World Health Organization 2016 Classification, glioblastoma, anaplastic astrocytoma, and anaplastic oligodendroglioma were present in nine, six, and five of the recruited patients, respectively. Gross total resection, partial resection, and biopsy were performed in four, nine, and seven patients, respectively. All patients received concurrent and adjuvant chemotherapy using temozolomide with or without bevacizumab. The completion rate of IMRT was 100%. The median follow-up period was 29 months (range=6-68 months). Median OS and PFS were 30 and 14 months, respectively. No patients experienced Grade 3 or higher non-hematological toxicity. The 2-year OS rates were 100%, 57%, and 33% in Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) classes I/II, IV, and V, respectively (p=0.002; log-rank test). CONCLUSION: IMRT using the standard radiation dose in patients with HGG can be carried out safely. RTOG-RPA class appears to be useful to estimate patient prognoses.

A retrospective study of locally advanced cervical cancer cases treated with CT-based 3D-IGBT compared with 2D-IGBT.

PURPOSE: To retrospectively review locally advanced cervical cancer (CC) cases treated with three-dimensional image-guided brachytherapy (3D-IGBT) and two-dimensional (2D)-IGBT. MATERIALS AND METHODS: Patients with Stage IB-IVa CC who underwent intracavitary irradiation between 2007 and 2021 were divided into the 3D-IGBT and 2D-IGBT groups. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and gastrointestinal toxicity (G3 or more) were investigated at 2/3 years post-treatment. RESULTS: Seventy-one patients in the 2D-IGBT group from 2007 to 2016 and 61 patients in the 3D-IGBT group from 2016-2021 were included in the study. The median follow-up period was 72.7 (4.6-183.9) months in the 2D-IGBT group and 30.0 (4.2-70.5) months in the 3D-IGBT group. The median age was 65.0 (40-93) years in the 2D-IGBT group and 60.0 (28-87) years in the 3D-IGBT group, but there was no difference in FIGO stage, histology, or tumor size between the groups. In treatment, the median A point dose was 56.1 (40.0-74.0) Gy in the 2D-IGBT group and 64.0 (52.0-76.8) Gy in the 3D-IGBT group (P < 0.0001), and the proportion of patients who underwent chemotherapy more than five times was 54.3% in the 2D-IGBT group and 80.8% in the 3D-IGBT group (P = 0.0004). The 2/3-year LC, DMFS, PFS, and OS rates were 87.3%/85.5%, 77.4%/65.0%, 69.9%/59.9%, and 87.9%/77.9% in the 2D-IGBT group, and 94.2%/94.2%, 81.8%/81.8%, 80.5%/80.5%, and 91.6%/83.0% in the 3D-IGBT group, respectively. A significant difference was observed in PFS (P = 0.02). There was no difference in gastrointestinal toxicity, but there were four intestinal perforations in the patients from the 3D-IGBT group, three of whom had a history of bevacizumab treatment. CONCLUSION: The 2/3-year LC of the 3D-IGBT group was excellent and PFS also tended to improve. Care should be taken with concomitant use of bevacizumab after radiotherapy.

Prospective Exploratory Study of the Relationship Between Radiation Pneumonitis and TGF-ß1 in Exhaled Breath Condensate.

BACKGROUND/AIM: We conducted a prospective exploratory study to investigate the relationship between radiation pneumonitis (RP) and transforming growth factor-ß1 (TGF-ß1) in exhaled breath condensate (EBC). PATIENTS AND METHODS: The inclusion criteria were: patients who 1) received thoracic radiotherapy (RT) for lung cancer, 2) were aged ≥20 years, and 3) provided written informed consent. EBC was collected before and 1 month after RT. TGF-ß1 levels in EBC were measured using an enzyme-linked immunosorbent assay. We evaluated RP using the Common Terminology Criteria for Adverse Events v4 and analyzed the relationship between grade (G) 2 RP and TGF-ß1 levels in EBC. RESULTS: Ten patients were enrolled [median age, 75 years (range=60-81 years)], and none of them had interstitial lung disease. Conventional fractionation, accelerated hyperfractionation, hypofractionation, and stereotactic ablative fractionation were used in four, one, two, and three patients, respectively. G1 and G2 RP were observed in five patients each; no G3-G5 RP occurred. The median TGF-ß1 levels in EBC before and 1 month after RT were 79.1 pg/ml (0.1-563.7 pg/ml) and 286.9 pg/ml (33.7-661.3 pg/ml), respectively. Of the seven patients with increased TGF-ß1 levels in EBC 1 month after RT than before RT, five (71%) experienced G2 RP, whereas the remaining three patients with decreased TGF-ß1 levels had G1 RP (p=0.083, one-sided Fisher's exact test). CONCLUSION: Increased TGF-ß1 levels in EBC 1 month after RT might be promising for the detection of G2 RP.

Target coverage of daily cone-beam computed tomography in breath-hold image-guided radiotherapy for gastric lymphoma.

OBJECTIVES: We evaluated retrospectively the daily target coverage using cone-beam computed tomography (CBCT) in breath-hold image-guided radiotherapy (BH-IGRT) for gastric lymphoma. METHODS: BH-IGRT was performed using a prescribed dose of 30.6 Gy in 17 fractions for the whole stomach. We assessed the target coverage of the whole stomach on daily CBCT images [daily clinical target volume (CTV)], which was delineated individually by two observers. We evaluated V95% (percentage of volume receiving ≥95% of the prescribed dose) of daily CTV. RESULTS: In total, 102 fractions from 6 patients were assessed. The mean V95% of daily CTV was 97.2%, which was over 95%. In two of six patients, the V95% of daily CTV was over 95% for either observer in all fractions. One patient had significant interobserver variation (p = 0.013). In 95 fractions (93%), the V95% of daily CTV was over 95% for either observer. CONCLUSION: Daily target coverage for CTV in BH-IGRT for gastric lymphoma seems to be favorable, even when using CBCT. ADVANCES IN KNOWLEDGE: A previous study ascertained good daily target coverage in BH-IGRT for gastric lymphoma using in-room CT. Even when using CBCT in our study, daily target coverage for CTV in BH-IGRT for gastric lymphoma seems to be favorable.

Feasibility of hippocampal dose-volume parameters associated with memory decline in intensity-modulated radiotherapy for supratentorial tumors.

The purpose of the present retrospective study was to evaluate the feasibility of hippocampal dose-volume parameters associated with memory decline for intensity-modulated radiotherapy (IMRT). In total, 18 patients who underwent IMRT for supratentorial tumors were analyzed. Prescribed doses of IMRT in 30 fractions were 60 Gy to planning target volume (PTV) 1 of the local area and 48-51 Gy to PTV2 of the extended local area. Based on previous literature, the present study investigated dose-volume parameters of the bilateral hippocampi: D40% of 13.1 Gy, D50% of 29.6 Gy, and V55Gy of 5.0%. It was evaluated which of the parameters was most achievable, and unfavorable factors that interfere with reaching these parameters were identified. As a result, D40% of 13.1 Gy, D50% of 29.6 Gy and V55Gy of 5.0% were achieved in 17, 67 and 33% of patients, respectively. For D50% of 29.6 Gy, PTV2 ≥500 cc (P=0.004) and tumor in temporal/corpus callosum/basal ganglia (P=0.009) were significant unfavorable factors. In conclusion, D50% of 29.6 Gy was most achievable. In daily clinical practice, it should be primarily attempted to achieve D50% of 29.6 Gy of the bilateral hippocampi.

Correlation of Pathological Complete Response With Tumor Volume Reduction During Neoadjuvant Chemoradiotherapy in Lung Cancer.

BACKGROUND/AIM: We retrospectively investigated the relationship between pathological complete response (pCR) and tumor volume (TV) reduction during neoadjuvant chemoradiation therapy (NACRT) in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We evaluated patients who received NACRT (50 Gy/25 fractions with platinum-doublet) plus surgery for NSCLC. TVs before and during NACRT (TVbefore and TVduring, respectively) were measured based on the sums of the volumes of primary tumors and clinically positive lymph nodes. Relative change in TV was computed as % (TVduring - TVbefore)/TVbefore Results: In total, 31 patients were analyzed. The median of the relative change in TV was - 49% and ranged from -83 to -10%. Postoperatively, pCR was achieved in 11 patients (35%). In multivariate analysis, the relative change in TV was found to be an independent predictor of pCR (p=0.003). CONCLUSION: TV reduction during NACRT appears to be associated with pCR in NSCLC.

Comparison Between Stereotactic and Conventional Radiotherapy for Solitary Lung Tumor After Resection of Lung Cancer.

BACKGROUND/AIM: We retrospectively compared stereotactic body radiotherapy (SBRT) with conventionally fractionated radiotherapy (CFRT) for a solitary lung tumor after resection of a non-small cell lung cancer (NSCLC), due to a lack of data concerning whether SBRT or CFRT is more effective in this setting. PATIENTS AND METHODS: SBRT using 48 Gy in 4 fractions was administered to 15 patients with a peripheral tumor (SBRT group). CFRT using 66-70 Gy in 33-35 fractions was administered to 11 patients with a central tumor (CFRT group). RESULTS: The median follow-up time was 32 months (range: 9-79 months). The 3-year overall survival rates in SBRT and CFRT groups were 81% and 40%, respectively (p=0.008). The 3-year local control rates in SBRT and CFRT groups were 83% and 35%, respectively (p=0.035). Regarding toxicities, no significant differences were found between the two groups. CONCLUSION: Compared to CFRT, SBRT may be more effective in solitary-lung-tumor patients after the complete resection of an NSCLC as with inoperable-stage I-NSCLC patients.

Differences in gross tumor volumes for pancreatic cancer: a comparison of ungated positron emission tomography and contrast-enhanced four-dimensional computed tomography.

PURPOSE: We assessed differences in gross tumor volumes (GTVs) for pancreatic cancer between respiratory-ungated positron emission tomography (3D-PET) and contrast-enhanced four-dimensional computed tomography (CE-4DCT). MATERIALS AND METHODS: We evaluated the GTVs in 21 patients. The sum of the GTVs, which was individually delineated by observers 1 and 2 on the CE-4DCT images from all respiratory phases, was used as GTV-4DCT. The GTVs on the 3D-PET images were extracted with three thresholds: 20%, 30%, and 40% of maximum activity concentration (GTV-n%). We selected one of the GTV-n%, which mostly resembled GTV-4DCT in size, as GTV-PET. Differences in the GTVs were analyzed. RESULTS: Median values of GTV-4DCT for observers 1, 2, and GTV-PET were 55.0 mL, 45.7 mL, and 14.6 mL, respectively. GTV-PET was smaller than GTV-4DCT for observers 1 and 2 (p < 0.01 each). Differences of median values of maximum diameters between GTV-4DCT and GTV-PET were 1.7-1.8 cm, 1.4-1.6 cm, and 1.9-2.1 cm in the left-right, anterior-posterior, and craniocaudal directions, respectively. CONCLUSION: GTV-PET based on 3D-PET images was smaller than GTV-4DCT for pancreatic cancer. When we refer to 3D-PET images without CE-4DCT images, we need to pay attention to the above-mentioned finding to contour the GTV.

Respiratory motion of lymph node stations in pancreatic cancer: Analyses using contrast-enhanced four-dimensional computed tomography.

BACKGROUND AND PURPOSE: Data regarding respiratory motion of lymph node (LN) stations in pancreatic cancer is limited. Therefore, we assessed their respiratory motion using contrast-enhanced four-dimensional-computed tomography (CE-4DCT). MATERIAL AND METHODS: We evaluated respiratory motion in 18 pancreatic cancer patients. We selected LN stations around major arteries which were visible on CE-4DCT images. This included the common hepatic, celiac, splenic, and superior mesenteric stations. Two radiation oncologists individually delineated the gross tumor volume (GTV) and the LN stations as observers 1 and 2. RESULTS: The respiratory motion of the celiac (median, 3.9 mm each for both observers) and superior mesenteric (median, 4.5 and 5.0 mm for observers 1 and 2, respectively) stations in the craniocaudal (CC) directions was significantly smaller than that of the GTV (median, 8.9 and 7.8 mm for observers 1 and 2, respectively). The respiratory motion of the common hepatic station (median, 3.8 and 3.6 mm for observers 1 and 2, respectively) in the anterior-posterior (AP) direction was significantly larger than that of the GTV (median, 2.8 and 2.2 mm for observers 1 and 2, respectively). CONCLUSIONS: We observed significant differences in respiratory motion between the GTV and the LN stations in pancreatic cancer.

Definitive concurrent chemoradiotherapy in a patient with stage IV non-small cell lung cancer due to cervical lymph node metastases.

In the American Society of Clinical Oncology guideline, it is mentioned that systemic therapy is a standard treatment, but there is no cure for patients with stage IV non-small cell lung cancer (NSCLC). Recent technical advances have facilitated the delivery of curative-intent radiation doses to some stage IV patients. In this report, we introduce a long-term disease-free survivor after concurrent chemoradiotherapy (CRT) and discuss considerations for this treatment. The patient was a 61-year-old woman diagnosed with stage IV adenocarcinoma of the lung classified as cT4N3M1c; the M1c classification was because of multiple synchronous pathologically proven cervical lymph node metastases (CLNM). We administered concurrent CRT to all lesions with a dose of 60 Gy in 30 fractions over 6 weeks. Concurrent chemotherapy consisted of two cycles of carboplatin and pemetrexed. Adjuvant chemotherapy was performed with five cycles of carboplatin and pemetrexed followed by three cycles of pemetrexed alone. As of 43 months after CRT, the patient was still alive without disease. In conclusion, our patient with stage IV NSCLC due to CLNM achieved long-term disease-free survival by concurrent CRT as with patients with locally advanced NSCLC. Patient subgroups should be explored to achieve long-term disease-free survival after definitive CRT in patients with stage IV NSCLC due to CLNM.

A Case of Spontaneous Tumor Lysis Syndrome in a Patient with Ovarian Cancer.

Tumor lysis syndrome (TLS) is a potentially life-threating complication of tumors or chemotherapy treatment. TLS commonly occurs in hematological malignancies, but it is very rare in patients with a solid tumor. In cases of solid tumors, TLS usually occurs spontaneously and after the initiation of anticancer therapy, and it has a high mortality rate. We present the novel case of a 62-year-old woman with an ovarian tumor who spontaneously developed TLS. Surgical reduction of the tumor mass vastly improved her condition. She showed no sign of tumor recurrence 8 months after treatment. As TLS is life-threatening, successful treatments must be seriously considered.