Comparison of acute toxicities between contemporary forward‐planned 3D conformal radiotherapy and inverse‐planned intensity‐modulated radiotherapy for whole breast radiation

The use of inverse‐planned intensity‐modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward‐planned field‐in‐field 3D conformal radiotherapy and tangential inverse‐planned intensity‐modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward‐planned field‐in‐field 3D conformal radiotherapy or intensity‐modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field‐in‐field 3D conformal radiotherapy and intensity‐modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity‐modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first‐line use of field‐in‐field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity‐modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity‐modulated radiotherapy.     

Chemical‐ and radiation‐induced haemorrhagic cystitis: current treatments and challenges

• To review the published data on predisposing risk factors for cancer treatment‐induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition.
• Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK‐led guidelines available on how it should optimally be defined and managed.
• A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment‐induced HC.
• There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria.
• The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette‐Guérin, where the incidence has been reported as up to 30%.
• Mesna (2‐mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment‐related cystitis, but are not always effective.
• Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited.
• The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option.
• The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC.

     

Outcomes with intraoperative radiation therapy for early‐stage breast cancer

Adjuvant radiation therapy has been associated with improved local control following breast‐conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3‐6 weeks or partial breast irradiation over 1‐3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early‐stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I‐II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x‐ray. Patients were treated at a single institution between 2011 and 2019. Follow‐up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow‐up of 23 months (range: 0‐73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor‐positive, 175 (87.9%) progesterone receptor‐positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low‐risk patients, demonstrated low rates of recurrence and reproducibility in a multi‐disciplinary setting. Further follow‐up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.     

The efficacy and safety of hypofractionated radiotherapy with concurrent anti‐HER‐2 therapy following breast‐conserving therapy for breast cancer

The purpose of this study was to report rates and severities of radiation‐related toxicities and analyze disease‐control outcomes in patients who have received hypofractionated whole breast radiation (HF) with concurrent trastuzumab with or without pertuzumab. We conducted a retrospective cohort study including women with stage I‐III HER2‐positive breast cancer who received HF at the University of Pennsylvania between 1/2005 and 5/2018 with concurrent trastuzumab with or without pertuzumab. Fractionation was 266 cGy daily to a total dose of 4256 cGy with or without a sequential tumor bed boost. Eighty patients were included in the cohort with a median follow‐up time of 21.44 months. There was one grade 3 acute toxicity (fatigue) and no grade 3 late toxicities. 91% and 25% of patients experienced grade 1‐2 acute and late skin reactions, respectively. An excellent‐good cosmetic outcome was reported by 74% and 95% of patients and physicians, respectively. No patients experienced tumor recurrences, and the only death was due to a secondary cause. These results suggest that hypofractionated whole breast radiation administered concurrently with anti‐HER‐2 therapies is efficacious and has acceptable toxicity in early‐stage breast cancer patients treated with lumpectomy. Continued follow‐up is warranted to evaluate long‐term outcomes.     

Impact of Surgery‐Radiation Interval on Locoregional Outcome in Patients Receiving Neo‐adjuvant Therapy and Mastectomy

Delays in the initiation of radiation are increasingly common for medically underserved patients. We evaluated the impact of delay in initiation of postmastectomy radiation (PMRT) in breast cancer patients treated with neo‐adjuvant therapy (NAT) in a cohort of medically underserved patients with multiple barriers to timely care. We retrospectively reviewed medical records of 248 consecutively treated patients. Clinical stage was 34.4% II, 65.6% III. The median interval from surgery to PMRT was 11.9 weeks; 22.2% started PMRT within 8 weeks of surgery, 52% within 12 weeks, and 67.3% within 16 weeks. The cumulative 5‐year incidence of locoregional recurrence (LRR) was 5.8% (95% CI: 3.2–9.7). There was no significant difference in locoregional outcome among patients starting PMRT within 8 weeks versus >8 weeks (p = 0.634), ≤12 versus >12 weeks (p = 0.332), or ≤16 versus >16 weeks (p = 0.549) after surgery. Although timely initiation of PMRT remains a priority, the locoregional control benefit of PMRT appears to be maintained up to at least 16 weeks, and in those without early locoregional recurrence, PMRT should be offered despite such a delay.     

Intraoperative radiation therapy for breast cancer—Immediate and 30‐month oncological outcomes

There is growing evidence that intraoperative radiation therapy (IORT) may be a viable option in selected patients with early breast cancer. This study reports our 4‐year experience with IORT. The perioperative outcome and imaging data of all patients who underwent IORT for early breast cancer at a tertiary medical center in 2014‐2018 were retrospectively retrieved. The cohort included 158 patients aged 52‐84 years (mean 68) with stage I (n = 137) or II (n = 21) breast cancer. Mean applicator size was 4.13 cm; IORT added a mean of 29 minutes to the operative time. Minor wound infections (n = 18, 11.4%) requiring antibiotics and drainage were the only postoperative complication. In 25 patients (15%), postoperative mammography demonstrated a seroma (n = 22) or fat necrosis (n = 3). The risk of wound infection or a new postoperative imaging finding was unrelated to patient age, operative time, tumor size, or comorbid diabetes or obesity. After a mean of 30 months' follow‐up, none of the patients who met the institutional criteria for IORT had local recurrence, regardless of age, histology, tumor grade, KI67 proliferation index, pathologic stage, Recurrence Score, or additional whole‐breast irradiation or adjuvant treatment. Patients for whom a Recurrence Score was determined (n = 55, 35%) had a significantly higher tumor grade, pathologic stage, and whole‐breast irradiation/adjuvant chemotherapy rate than the remaining patients. IORT may be a safe alternative to traditional external beam radiation in well‐selected patients with early breast cancer, with few minor complications and good 30‐month outcome.     

Post‐mastectomy radiation in node‐positive breast cancer in Ontario

More recent guidelines are more supportive for post‐mastectomy radiation in all node‐positive breast cancer patients. We examined the rate and predictors of post‐mastectomy radiation receipt in Ontario Canada from 2010 to 2014. Of 6535 node‐positive post‐mastectomy patients, 73.9% received radiation. The rate was 68.7% (2903/4227) among women with 1‐3 positive nodes. Radiation was less likely to be administered to women who were older, had high levels of comorbidity, or presented with early stages of breast cancer. Regional practice variation was reassuringly modest.