Does external beam radiation boost to pelvic lymph nodes improve outcomes in patients with locally advanced cervical cancer?

BACKGROUND: Current recommendation for locally advanced cervical cancer includes pelvic external beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy. Involvement of pelvic lymph nodes is an important prognostic factor in locally advanced cervical cancer and recurrence commonly occurs despite definitive treatment. To date, there is no standard guideline on whether an EBRT boost should be applied to involved pelvic lymph nodes. Our study aims to assess if pelvic EBRT boost would reduce recurrence, benefit survival, and affect associated toxicities. METHODS: We conducted a retrospective review of locally advanced cervical cancer cases treated with definitive treatment at our institution. Involvement of pelvic lymph nodes were assessed on CT, MRI (> 10 mm or suspicious features) or PET scan (SUVmax > 2.5). EBRT dose ranged from 45 to 50.4 Gy with nodal boost ranging from 3.6-19.8 Gy. RESULTS: Between 2008 to 2015, 139 patients with locally advanced cervical cancer underwent treatment. Sixty-seven patients had positive pelvic lymph nodes, of which 53.7% received a nodal boost. Five-year recurrence free survival was 48.6% with vs. 64.5% without nodal boost (P = 0.169) and 5-year overall survival in those with positive pelvic lymph nodes was 74.3% with vs. 80.6% without nodal boost (P = 0.143). There was no significant difference in toxicity with nodal boost. CONCLUSIONS: EBRT boost to pelvic lymph nodes does not reduce recurrence or improve survival in locally advanced cervical cancer with lymph node involvement at diagnosis.

Neuroblastoma in Children Under 12 Months in Singapore--15-Year Experience and Outcomes From KKH.

BACKGROUND: Expectant observation of small adrenal lesions has shown promising results in recent studies. We present our 15 years outcome of managing infant neuroblastoma. METHODS: All patients with neuroblastoma below the age of 1 year treated at the largest pediatric hospital in Singapore between 1998 and 2012 were identified. RESULTS: Twenty-two patients were included in our study. Six were antenatally diagnosed. Nineteen (86%) patients had surgical resection of the tumor. Eight (36%) patients received chemotherapy as part of their treatment. Six patients were observed three of which had large adrenal tumors. Median follow-up in our series was 2.6 years. The 5 year overall survival was 90%. There were no recurrences and there were 2 deaths in our series. CONCLUSION: Our series shows excellent outcomes of infant neuroblastoma at our center. Careful observation of large tumors may be an option to avoid the morbidity of surgery.

Splenic irradiation contributes to grade ≥ 3 lymphopenia after adjuvant chemoradiation for stomach cancer.

Introduction: Adjuvant chemoradiation therapy (CRT) in gastric cancer inevitably results in an unintentional spleen radiation dose. We aimed to determine the association between the spleen radiation dose and the observed severity of lymphopenia which may affect the clinical outcomes (survival time and infection risk). Methods: Patients who received adjuvant CRT for gastric cancer between January 2015 and December 2020 were analyzed. The splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least × Gray (Gy). Peripheral blood counts were recorded pre- and post-CRT. The development of severe (Common Terminology Criteria for Adverse Events, version 5.0, grade ≥ 3) post-CRT lymphopenia (absolute lymphocyte count [ALC] < 0.5 K/µL) was assessed by multivariable logistic regression using patient and dosimetric factors. Overall survival (OS), recurrence-free survival (RFS), and cumulative incidence of infectious events were estimated and analyzed using the Cox model or competing risk analysis. Results: Eighty-four patients with a median follow-up duration of 42 months were analyzed. Pre- and post-CRT median ALC values were 1.8 K/µL (0.9-3.1 K/µL) and 0.9 K/µL (0.0-4.9 K/µL), respectively (P < 0.001). MSD > 40 Gy (odds ratio [OR], 1.13; 95 % confidence interval [CI], 1.01-1.26; P = 0.041), sex (OR for male to female, 0.25; 95 % CI, 0.09-0.70; P = 0.008), and baseline absolute neutrophil count (OR per 1 unit increase, 1.61; 95 % CI, 1.02-2.58; P = 0.040) were associated with the development of severe post-CRT lymphopenia, which was a risk factor for poorer OS (hazard ratio [HR] = 2.47; 95 % CI, 1.24-4.92; P = 0.010) and RFS (HR = 2.27; 95 % CI, 1.16-4.46; P = 0.017). The cumulative incidence of infections was higher among severe post-CRT lymphopenia patients (2.53, 95 % CI, 1.03-6.23, P = 0.043). Conclusion: High splenic radiation doses increase the odds of severe post-CRT lymphopenia, an independent predictor of lower OS and higher risks of recurrence and infections in gastric cancer patients receiving adjuvant CRT. Therefore, optimizing the splenic DVH parameters may decrease the risk of severe post-CRT lymphopenia.

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01).

PURPOSE: Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC). METHODS AND MATERIALS: Patients were enrolled at de-escalating dose levels of wP (part A), starting at 80 mg/m2, concurrent with fixed-dose LDFWART delivered in 60 cGy fractions twice-daily, 2 days per week, for 6 continuous weeks. After completing the 6-week course of wP + LDFWART, patients received wP until disease progression. Dose-limiting toxicity was evaluated during the first 3 weeks of wP + LDFWART. At wP (80 mg/m2) + LDFWART, no dose-limiting toxicities were observed; this was the established maximum tolerated dose. The trial was expanded (part B) with 7 additional patients with platinum-resistant, high-grade serous ovarian cancer to confirm toxicity and activity. RESULTS: A total of 10 heavily pretreated patients were recruited (3 patients to part A, 7 patients to part B). They had received a median of 5 prior lines of therapy, and 70% of patients had received prior wP; 60% of patients completed 6 weeks of wP + LDFWART. Common related grade ≥3 adverse events were neutropenia (60%) and anemia (30%). Median progression-free survival was 3.2 months, and overall survival was 13.5 months. Of patients evaluable for response, 33% (3 of 9) achieved confirmed biochemical response (CA125 decrease >50% from baseline), 11% (1) achieved a partial response, and 5 patients had stable disease, giving a disease control rate of 66.7% (6 of 9). Four patients had durable disease control of ≥12 weeks, completing 12 to 21 weeks of wP. CONCLUSIONS: The recommended phase 2 dose of wP + LDFWART for 6 weeks is 80 mg/m2. Encouraging efficacy in heavily pretreated PROC patients was observed, suggesting that further development of this therapeutic strategy in PROC should be considered.

Automatic quantification of calcifications in the coronary arteries and thoracic aorta on radiotherapy planning CT scans of Western and Asian breast cancer patients.

PURPOSE: This study automatically quantified calcifications in coronary arteries (CAC) and thoracic aorta (TAC) on breast planning computed tomography (CT) scans and assessed its reproducibility compared to manual scoring. MATERIAL AND METHODS: Dutch (n = 1199) and Singaporean (n = 1090) breast cancer patients with radiotherapy planning CT scan were included. CAC and TAC were automatically scored using deep learning algorithm. CVD risk categories were based on Agatson CAC: 0, 1-10, 11-100, 101-400 and >400. Reliability between automatic and manual scoring was assessed in 120 randomly selected CT scans from each population, with linearly weighted kappa for CAC categories and intraclass correlation coefficient for TAC. RESULTS: Median age was higher in Dutch patients than Singaporean patients: 57 versus 52 years. CAC and TAC increased with age and were more present in Dutch patients than Singaporean patients: 24.2% versus 17.3% and 73.0% versus 62.2%, respectively. Reliability of CAC categories and TAC was excellent in the Netherlands (0.85 (95% confidence interval (CI) = 0.77-0.93) and 0.98 (95% CI = 0.96-0.98) respectively) and Singapore (0.90 (95% CI = 0.84-0.96) and 0.99 (95% CI = 0.98-0.99) respectively). CONCLUSIONS: CAC and TAC prevalence was considerable and increased with age. Deep learning software is a reliable method to automatically measure CAC and TAC on radiotherapy breast CT scans.

Novel anesthetic technique for combined intracavitary and interstitial brachytherapy for cervix cancer in an outpatient setting.

PURPOSE: To determine the feasibility and safety of outpatient combined intracavitary and interstitial brachytherapy for cervix cancer with sedation and local anesthesia. MATERIAL AND METHODS: We included patients diagnosed with non-metastatic cervix cancer and have completed brachytherapy between December 2015 and December 2016. Moderate to deep sedation was achieved using intravenous midazolam, propofol, fentanyl, and oxycodone. Local anesthesia was achieved with 2% lignocaine gel and a paracervical block containing a mixture of 1% ropivacaine, 2% lignocaine, and 1 : 1,000 adrenaline. Ceftriaxone and ondansetron were given prophylactically. Physiologic monitoring was performed throughout and pain scores were recorded using the Numeric Rating Scale. Follow-up was conducted at 8 weeks from the last fraction of brachytherapy. The feasibility and safety endpoints were a post-anesthesia discharge score (PADS) of 9 or above, and no grade 3 or above adverse events, respectively. RESULTS: A total of thirty-five brachytherapy insertions were carried out on nine patients. The median age of the patients was 56 years (range, 40-65). Eight patients had American Society of Anesthesiologists' physical status of I or II, and one had a status of III. The mean duration of the insertion was 39 minutes (standard deviation [SD] = 14), during which no adverse events occurred. There was no significant nausea or vomiting post-sedation. The median pain scores post-insertion and during recovery were 0 (range, 0-6) and 0 (range, 0-7), respectively. At discharge, all patients had pain scores of 0 and maximum PADS of 10. The mean time to discharge was 4.1 hours (SD = 0.95). There were no brachytherapy-related admissions or complications. CONCLUSIONS: Outpatient combined intracavitary and interstitial brachytherapy for cervix cancer with sedation and local anesthesia is feasible and safe. This could potentially lead to significant cost savings.

Feasibility study of toxicity outcomes using GEC-ESTRO contouring guidelines on CT based instead of MRI-based planning in locally advanced cervical cancer patients.

PURPOSE: To report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Between 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: The median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity. CONCLUSIONS: Despite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities.

Outpatient combined intracavitary and interstitial cervical brachytherapy: barriers and solutions to implementation of a successful programme - a single institutional experience.

Involvement of parametrial disease in locally advanced cervical patients poses a challenge for women undergoing brachytherapy. Current use of the Fletcher suit applicator may not adequately cover the high risk clinical target volume (HR CTV), especially in the parametrial region due to the physical qualities of brachytherapy from the inverse square law and the need to respect organs at risk (OAR) constraints, and leads to lower local control rates. Combined intracavitary and interstitial brachytherapy with the use of 1 or 2 interstitial needles allows adequate coverage of the HR CTV and the clinical evidence have demonstrated a correlation with better clinical results. This procedure is often resource intensive, requiring inpatient stay and magnetic resonance imaging (MRI) planning. In departments where such resources are limited, there is a poor uptake of interstitial brachytherapy. This article discusses the technique of combined intracavitary and interstitial brachytherapy in an outpatient setting, and explores the issues and barriers for implementation and suggestions to overcome such barriers.

Multi-catheter interstitial accelerated partial breast irradiation - tips and tricks for a good insertion.

Adjuvant radiotherapy is recommended post breast conserving surgery. Accelerated Partial Breast Irradiation (APBI) offers a more attractive shorter course of treatment over 5 days compared to standard conventional external beam radiotherapy, which is often protracted. Multi-catheter interstitial APBI offers excellent dosimetric coverage. This article describes two insertion techniques for multi-catheter interstitial APBI, the operator dependent freehand technique, and the easier to learn template technique. The indications, benefits, and drawbacks of these two techniques are discussed.

Comparing a volume based template approach and ultrasound guided freehand approach in multicatheter interstitial accelerated partial breast irradiation.

PURPOSE: Currently, there are two described methods of catheter insertion for women undergoing multicatheter interstitial accelerated partial breast irradiation (APBI). These are a volume based template approach (template) and a non-template ultrasound guidance freehand approach (non-template). We aim to compare dosimetric endpoints between the template and non-template approach. MATERIAL AND METHODS: Twenty patients, who received adjuvant multicatheter interstitial APBI between August 2008 to March 2010 formed the study cohort. Dosimetric planning was based on the RTOG 04-13 protocol. For standardization, the planning target volume evaluation (PTV-Eval) and organs at risk were contoured with the assistance of the attending surgeon. Dosimetric endpoints include D90 of the PTV-Eval, Dose Homogeneity Index (DHI), V200, maximum skin dose (MSD), and maximum chest wall dose (MCD). A median of 18 catheters was used per patient. The dose prescribed was 34 Gy in 10 fractions BID over 5 days. RESULTS: The average breast volume was 846 cm(3) (526-1384) for the entire cohort and there was no difference between the two groups (p = 0.6). Insertion time was significantly longer for the non-template approach (mean 150 minutes) compared to the template approach (mean: 90 minutes) (p = 0.02). The planning time was also significantly longer for the non-template approach (mean: 240 minutes) compared to the template approach (mean: 150 minutes) (p < 0.01). The template approach yielded a higher D90 (mean: 95%) compared to the non-template approach (mean: 92%) (p < 0.01). There were no differences in DHI (p = 0.14), V200 (p = 0.21), MSD (p = 0.7), and MCD (p = 0.8). CONCLUSIONS: Compared to the non-template approach, the template approach offered significant shorter insertion and planning times with significantly improved dosimetric PTV-Eval coverage without significantly compromising organs at risk dosimetrically.

Body mass index and patient CT measurements as a predictor of benefit of intensity-modulated radiotherapy to the supraclavicular fossa.

BACKGROUND: Irradiation of the supraclavicular fossa is commonly used as part of adjuvant breast radiotherapy. Intensity-modulated radiotherapy (IMRT) may be used to target this region accurately, and there are subgroups of patients that may benefit more from IMRT than others. We identify the benefit of IMRT over fixed-depth dose prescription to the supraclavicular fossa in patients of different builds in a clinical setting. METHODS: Fifteen patients who received radiotherapy to the left breast and supraclavicular fossa were selected. Computed tomographic planning was used to generate plans for supraclavicular fossa coverage. Dose prescription to 1.5 cm and 3.0 cm depths was compared with IMRT plans. Coverage of the planning target volume and dose to the organs at risk were compared and correlated with patient body mass index (BMI) and computed tomography measurements. RESULTS: Within the IMRT group, increasing depth of the supraclavicular fossa produced significantly better coverage of the planning target volume with IMRT. IMRT resulted in lower mean doses to the brachial plexus (P = 0.00) when compared with 1.5 cm and 3 cm depth dose prescriptions, but higher maximum brachial plexus doses. IMRT was more beneficial in patients with lower BMI because this resulted in a decreased maximum brachial plexus dose (P-values of 0.03 and 0.001 when compared with 1.5 cm and 3.0 cm depth dose prescriptions, respectively). Higher patient BMI resulted in a lower dose contribution of IMRT to the cord (P-values 0.066 and 0.034 when compared with 1.5 cm and 3.0 cm depth dose prescriptions respectively). CONCLUSION: IMRT of the supraclavicular fossa results in lower brachial plexus doses for patients with low BMI while patients with higher BMI benefit from lower mean cord doses. IMRT provides superior coverage of the planning target volume, especially in patients with a deeper supraclavicular fossa.