Anesthetic considerations for the pediatric oncology patient – part 1: a review of antitumor therapy

The anesthesiologist who cares for children with cancer or for survivors of childhood cancer should possess a basic understanding of cancer treatment. While this is an ever‐changing field, a basic knowledge of chemotherapeutic drugs, radiation therapy, and the toxicities of each is necessary to prepare a safe anesthetic plan. Such an understanding also assists the anesthesiologist as the perioperative specialist for these children in consultation with the surgeon and oncologist. This article, which is the first of a three‐part review series, will review current principles of cancer therapy and the general mechanisms of toxicity to the child. Although this article is not intended to comprehensively review the fundamentals of chemotherapy and radiation therapy, the consequences of anticancer therapy that impact perioperative care and decision making are presented for the anesthesiologist.     

Delayed onset of overt porphyria cutanea tarda in a patient on long-term haemodialysis. A case report

After 7 years on haemodialysis, a 37-year-old anephric man developed cutaneous lesions of the hands, arms and face, shown by skin biopsy to be compatible with porphyria cutanea tarda (PCT) (symptomatic porphyria). Elevated levels of plasma uroporphyrin and 7-COOH porphyrin were detected alongside a predominant isocoproporphyrin fraction in the faeces by means of quantitative thin-layer chromatography, confirming the diagnosis of overt PCT. The plasma uroporphyrin did not pass into the dialysate, even after chloroquine therapy. There was no evidence of hereditary PCT, chronic liver disease or iron overload, although the patient had a history of excessive alcohol consumption. The overt PCT developed after 8 months of home dialysis using softened water with high aluminium concentrations and subsided clinically and biochemically when the softened water was replaced by deionized water.     

Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy

Background

With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy.

Objective

Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting.

Design, setting, and participants

A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo.

Intervention

All patients were treated with SRT with either 3D-CRT (n = 109) or IMRT (n = 176). A total of 205 patients (72%) were treated with doses ≥70 Gy.

Measurements

Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition.

Results and limitations

The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p = 0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p = 0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p = 0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p = 0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up.

Conclusions

Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity.     

Haemoperitoneum due to ruptured hepatoma in a cirrhotic patient with porphyria cutanea tarda. Three years' survival (author's transl)

A case of ruptured hepatocarcinoma of the left lobe in a cirrhotic patient with a 7 years' history of porphyria cutanea tarda (PCT) is reported. Emergency left lobectomy resulted in 3 years' survival with no sign of recurrence at present. Comments are made concerning the clinical association PCT-hepatoma: (1) either PCT is associated with a hypersecretory hepatoma and behaves as a neoplastic syndrome following the same course as the tumour; (2) or PCT is associated with a cirrhosis (usually alcoholic) which facilitates the development of a hepatoma. In such cases, PCT precedes the tumour and follows a separate course.     

Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy

The purpose of this study was to describe the toxicity of concurrent standard dose adjuvant radiation therapy (RT) and paclitaxel in a series of patients receiving primary breast cancer therapy. From June 1998 to April 1999, 20 patients with breast cancer received concurrent adjuvant radiation and paclitaxel. There were 16 patients (80%) with American Joint Committee on Cancer (AJCC) stage II disease and 4 with stage III disease. Eighteen patients, 12 postmastectomy and 6 breast conservation, were treated with definitive surgery followed by concurrent RT and paclitaxel. Two received concurrent neoadjuvant radiation and paclitaxel. All patients received a doxorubicin-containing combination prior to radiation and paclitaxel. RT was delivered concurrently with paclitaxel after the completion of all doxorubicin therapy, with all patients receiving at least two cycles of paclitaxel (175 mg/m ²) every 3 weeks during RT. Toxicity was graded weekly according to Radiation Therapy Oncology Group criteria. Thirteen patients (65%) developed grade 2 or higher cutaneous toxicity. In the postmastectomy group, 6 of 12 patients (50%) developed grade 2 cutaneous toxicity, and 4 of 12 patients (33%) developed grade 3. RT was discontinued in 1 and placed on hold in 3 of these patients. In the breast-conservation group, 2 of 6 patients (33%) developed grade 3 toxicity. In the neoadjuvant group, 1 of 2 patients (50%) developed grade 3 toxicity. Four patients (20%) developed radiation pneumonitis, 2 of 12 (17%) in the postmastectomy group and 2 of 6 (33%) in the breast conservation group, with 2 requiring hospitalization and 1 a diagnostic open-lung biopsy. In this group of patients, standard dose concurrent radiation and paclitaxel resulted in a high incidence of cutaneous and pulmonary toxicity. Concurrent radiation and paclitaxel with these doses and schedule should be approached cautiously until further studies documenting its safety are completed.     

Anesthetic considerations for the pediatric oncology patient – part 2: systems‐based approach to anesthesia

One of the prices paid for chemo‐ and radiotherapy of cancer in children is damage to the vulnerable and developing healthy tissues of the body. Such damage can exist clinically or subclinically and can become apparent during active antineoplastic treatment or during remission decades later. Furthermore, effects of the tumor itself can significantly impact the physiologic state of the child. The anesthesiologist who cares for children with cancer or for survivors of childhood cancer should understand what effects cancer and its therapy can have on various organ systems. In part two of this three‐part review, we review the anesthetic issues associated with childhood cancer. Specifically, this review presents a systems‐based approach to the impact from both tumor and its treatment in children, followed by a discussion of the relevant anesthetic considerations.     

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.     

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.     

Effect of radiation therapy and Photofrin® on tissue response in a rat model

Treatment of advanced carcinomas of the head and neck may benefit from adjuvant photodynamic therapy and brachyradiotherapy. To date, however, there has been no controlled study to evaluate whether high-dose irradiation can be safely accomplished without major tissue reaction in the presence of high circulating doses of Photofrin, the photosensitizing agent used in photodynamic therapy. Thirty adult male white rats were involved in the study. Fifteen rats received Photofrin 5 mg/kg intravenously, and 15 rats received the same volume of sterile saline intravenously. At 48 hours following injection, each rat received 1,000 cGy of radiation to a 3 × 5 cm area of dorsal skin using a cobalt linear accelerator unit. Skin changes postradiation were observed for degree of erythema, blistering, necrosis, and sloughing. Five rats from the Photofrin and control radiation groups were sacrificed on days 2, 7, and 21 postradiotherapy. Skin changes in each animal were identical with mild erythema lasting from 10–14 days postradiotherapy. There was no evidence of blistering, necrosis, or sloughing of skin in any of the animals studied. Histologic evaluation of the irradiated skin after sacrifice demonstrated no difference between the Photofrin and saline-irradiated groups. As well, the histologic recovery from acute radiation injury was also identical. This controlled study demonstrates that radiation therapy may be safely administered without increased morbidity when tissue concentrations necessary to perform photodynamic therapy are present. © 1993 Wiley-Liss, Inc.     

Anesthetic considerations for the pediatric oncology patient – Part 3: pain,cognitive dysfunction,and preoperative evaluation

In part three of this three‐part review, we continue with discussion of the effects of tumor and its therapy as they impact neurocognitive functioning, psychosocial issues of the patient and family, and the mechanisms and experience of pain in the child with cancer. A discussion of preanesthetic testing and evaluation in this patient population is next presented for the reader, focusing on the factors which pose the commonest and greatest risks to the child undergoing surgery. Lastly, an algorithmic approach to evaluating and managing key components of the medical history of pediatric patients is presented.     

Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy for nonlocalized prostate cancer: a systematic review and meta-analysis

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT) alone versus combined with radiation therapy (RT) or chemotherapy for locally advanced and metastatic prostate cancer (PCa). A literature search was performed using OvidSP. Randomized controlled trials (RCTs) that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus docetaxel–estramustine (n = 413) in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall survival (OS) was 1.43 (95% confidence interval 1.20–1.71) when compared ADT plus RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01–1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.     

Anesthetic management of vaginal tear repair during early puerperium in a patient with acute intermittent porphyria

A 26 year old female with history of acute intermittent porphyria (AIP) was scheduled for vaginal tear repair after delivering her first baby. Raised blood pressure during her antenatal period was safely treated with α-methyl dopa. Her preoperative examination revealed no symptoms suggestive of acute exacerbation of AIP. Anesthesia was induced with fentanyl and propofol, and a proseal laryngeal mask airway (LMA) was inserted and maintained with intermittent propofol and inhalation of isoflurane in nitrous oxide and oxygen. Her intraoperative and postoperative period remained uneventful.