Virtual Library

Abstract:
Bronchoscopy dates back to the late 18th century where rigid illuminating tubes were used to examine the tracheobronchial tree. With the introduction of the fiberoptic bronchoscope, bronchoscopy has revolutionized the practice of pulmonary medicine. In lung cancer, due to advances in real-time imaging and catheter based techniques, bronchoscopy remains pivotal not only in diagnosis and staging, it also allows therapeutic intervention for airway restoration in patients with central airway obstruction, and treatment of early detected central airway cancers. For peripheral lung nodules that are beyond the visibility of the bronchoscope, computed tomography (CT) guided, navigational methods, and endobronchial ultrasonography (EBUS) facilitate accurate targeting. Since bronchoscopy allows access to the lung, it enables researchers to better understand lung carcinogenesis, discover biomarkers for early detection and prognostication as well as assess tumor response to targeted therapy by in-vivo microdynamic imaging. Pleuroscopy provides the physician a window to the pleural space by enabling biopsy of the parietal pleura under direct visual guidance in the evaluation of effusions of unknown etiology, guided chest tube placement, and talc pleurodesis as palliation of malignant pleural effusions. Cancer related pleural effusions occur as a result of direct tumor invasion, tumor emboli to the visceral pleura with secondary seeding of the parietal pleura, hematogenous spread, or via lymphatic involvement. Elastin staining and careful examination for invasion beyond the elastic layer of the visceral pleura should be carried out for lung cancer resections, as visceral pleural invasion is regarded as an important stage-defining feature in the absence of nodal involvement. Metastatic spread of lung cancer to the pleura adversely affects survival, and in the recent TNM staging of lung cancer, presence of pleural metastasis is defined as M1a (from T4), representing a corresponding change from stage IIIB to stage IV. It is rare to find resectable lung cancer in the setting of an exudative pleural effusion, despite negative cytologic examination. Thus, pleuroscopy can establish operative eligibility by determining if the pleural effusion is paramalignant or due to metastases. If pleural metastases are found, and therefore confirming inoperable disease, talc poudrage can be performed at the same setting. This has been shown to be more effective in preventing recurrence than intrapleural instillation of a sclerosant.

Abstract:
With the improvement of treatment efficacy, quality of life and sexual functioning after cancer treatment have become very important. Sexual well-being may be altered by both the diagnosis and the treatment of cancer. This in turn can have a deleterious impact on quality of life. Sexual dysfunction in cancer patients may result from biological, psychological and social factors (1). Biological factors such as anatomic alterations (rectum or penile amputation), physiological changes (hormonal status) and secondary effect of medical intervention may preclude normal sexual functioning even when sex desire is intact. Side effects of chemotherapy such as nausea, vomiting, fatigue, hair loss can result in adverse effects on sexuality together with disfiguring surgery (mastectomy, colostomy). Negative emotional states such as anxiety, depression, anger may also disrupt sexual activity (1). Disturbances of body image can contribute to the development of sexual dysfunction as well. Radiotherapy and radical prostatectomy are the most effective treatments for prostate cancer. Erectile dysfunction is reported in 6-80% after external-beam radiotherapy and 2-61% after brachytherapy. Erectile dysfunction after surgery is reported in 40-70% after nerve-sparing techniques and 100% in non-nerve-sparing techniques, and it occurs immediately after surgery. Ejaculation problems and libido decrease occur in up to 80%. Vascular, neurogenic and psychogenic factors are all important etiologic factors (1-3). Similar data are reported after treatment of bladder and colorectal cancer in males. Testicular cancer affects young men in their fertile and sexually active life. Retrograde ejaculation, erectile dysfunction, loss of libido, decreased orgasm and body image impairment are often reported after treatment (1,4). Surgery and radiotherapy for gynaecological cancer can alter vaginal sensation and may cause stenosis leading to painful penetration (1,3,5). These treatments lead to ovarian suppression, with vaginal discharge, dryness, dyspareunia and a loss of sexual interest. Only 50% of the females is still sexually active after cancer treatment (1). There is often fear of pain and of urine or faeces incontinence during sexual activity. Similar complaints are reported after treatment of colo-rectal and anal cancer in women. There is no data on the effects of treatment for lung cancer on sexual functioning. Though it is to be expected that these patients, both males and females, can report sexual dysfunction as a result of chemotherapy, social and psychological factors (distress, depression). For several reasons sexual counseling has not become a routine part of oncology care in most hospitals (6). There is a time constraint: in busy oncology clinics, where the outpatient visit is focused on addressing prognosis and treatment, physicians do not have time to assess quality of life. Another barrier is the discomfort physicians, and patients, have to discuss sexuality. The great majority of oncology professionals are scared to address sexuality and the great majority of sexological professionals are scared by cancer (7). Sexual counseling should be routinely provided in an oncology clinic having a health care professional (physician, or oncology nurse specialist) to evaluate and discuss quality of life matters, including sexual dysfunction, and possible treatments. In most cases patients do not require extensive medical or psychological treatments, but they need information about the impact of cancer treatment on sexuality (6). Patients, and partners, are often uninformed about the anatomy of sexual organs, therefore they have to be counseled on the effects that treatment has on the sexual organs. Several questionnaires are available to evaluate sexual functioning in both males and females (1). Recently a specific questionnaire on sexual functioning after treatment of cancer has been developed in the USA, but has not been validated yet in other countries (8). The 3rd International Consultation on Sexual Medicine appointed for the first time in 2009 a Committee on chronic illness (including cancer) and sexual medicine. The recommendations of that committee are very useful in helping to develop research programs in oncology and sexual medicine (9). Sexual dysfunction is often unrecognized, underestimated and untreated. Cancer affects quantity and quality of life. The challenge for physicians and other health care professionals is to address both components with compassion (7). References 1. Sadovsky R, Basson R, Krychman M, et al. Cancer and sexual problems. J Sex Med 2010;7:349-373. 2. Incrocci L, Slob AK, Levendag PC. Sexual (dys)function following radiotherapy for prostate cancer: a review. Int J Radiat Oncol Biol Phys 2002;52:681-693. 3. Incrocci L, Jensen PT. Pelvic radiotherapy and sexual function in men and women. J Sex Med 2013;10 Suppl 1:53-64. 4. Wortel RC, Ghidey WA, Incrocci L. Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective evaluation of short-term effects on body image and sexual function. J Sex Med 2015;12:210-218. 5. Jensen PT, Groenvold M, Klee MC, et al. Longitudinal study of sexual function and vaginal changes after radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2003;56:937-949. 6. Schover LR. Counseling cancer patients about changes in sexual function. Oncology 1999;11:1585-1591. 7. Incrocci L. Talking about sex to oncologists and cancer to sexologists. J Sex Med 2011;12:3251-3253. 8. Flynn KE, Lin L, Cyranowski JM, et al. Development of the NIH PROMIS® Sexual Function and Satisfaction measures in patients with cancer. J Sex Med 2013;10 Suppl 1:43-52. 9. Montorsi F, Adaikan G, Becher E, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2010;7:3572-3588.

Abstract:
Thoracic radiation therapy (RT) has been historically the first definitive therapy for Stage III non-small cell lung cancer (NSCLC), achieving median survival time (MST) of 10 months (mo). Adding chemotherapy extended MST to 13.8 mo (induction chemotherapy) or 17-20 mo. (concurrent chemotherapy) in randomized trials which used two-dimensional (2D) RT. Most recently, large randomized clinical trials for PET-staged patients treated with modern thoracic RT reported MST of 28.7 mo. (1). The reasons for such impressive survival improvement over last two decades are not fully understood and are likely multifactorial, including universal FDG-PET staging on presentation (therefore removing unsuspected Stage IV patients); progress in thoracic RT (precise target definition with CT simulation; widespread 3D RT or Intensity Modulated RT[IMRT], allowing volumetric rather than point radiation dose prescribing; heterogeneity correction accounting for different density of air vs. soft tissue; increased understanding of normal tissue tolerance, such as spinal cord, allowing relative sparing of lung parenchyma; image-guided RT minimizing normal tissue margins and “missed targets” etc.); widespread use of low-dose well-tolerated outpatient chemotherapy regimens; improved supportive care; effectiveness of second- and third-line systemic therapy etc. In a population study of >5,000 SEER-Medicare patients with NSCLC, wider adoption of CT simulation for thoracic RT planning was associated with improved overall survival (2). Local control rate was 70% at 2 years in the large cooperative group Phase III randomized trial (RTOG 0617) in the 60 Gy standard arms, defined as lack of tumor progression within the irradiated field. Most patients succumb to distant metastases which continue to be the leading cause of death of patients with lung cancer. Since death from distant metastases and local failure constitute competing risks, the likely incidence of local failure may be higher if longer overall survivals are achieved. The optimal RT dose allowing improved local control has not been fully established and the current recommendation is to use 60 Gy in daily 2 Gy fractions, with concurrent chemotherapy in fit patients. RT dose escalation to 74 Gy was associated with worse MST when compared to 60 Gy in a randomized trial (20.3 vs. 28.7 mo., respectively) (RTOG 0617). While the reasons for such worse survival are not clear, the possibilities include higher RT heart doses in the 74 Gy arm, greater number of deaths in the high-dose group, extended duration of radiation therapy to 7.5 weeks, and uncertainty about true causes of death (1). Nevertheless, efforts toward RT dose intensification continue, with particular attention given to the shortening of the overall treatment time through hypofractionation (for example, in the RTOG 1106 a mid-treatment PET-adapted hypofractionated RT boost is applied to the residual tumor volumes during a total duration of 30 RT fractions )(NCT01507428). While the proportion of patients with Stage III NSCLC receiving IMRT has been increasing as compared to 3D RT (3% in 2002 vs. 26.8% in 2009)(3), the superiority of IMRT has not been convincingly demonstrated. Among patients receiving potentially curative treatment, there was no difference in overall survival (propensity adjusted HR .99, p = 0.83) or number of hospital days in the 90 days following radiation start, as demonstrated by the SEER-Medicare analysis of over 7,000 patients. The technology currently being investigated involves proton therapy, which has been shown in treatment-planning comparisons to deliver high-dose, highly conformal radiation to targets while minimizing damage to surrounding normal tissues. In particular, the subclinical cardiovascular toxicity suspected to be detrimental in the RTOG 0617 trial, which might have accounted for worse survival in the high-dose arms, may be mitigated with protons due to their physical property of a sharp distal dose edge. Long term results from a prospective single institution study of 134 patients receiving concurrent proton thoracic RT (median dose: 74 Gy) and chemotherapy (4) demonstrated the MST of 40 mo. for Stage II NSCLC patients and 30 mo. for Stage III patients, and a local + marginal failure-free rate of approximately 50% at 5 years. Grade 2 radiation pneumonitis was reported in 29 (22%) patients and Grade 3, in 2(1.5%). An ongoing study, the NRG Oncology/RTOG 1308, is a phase III trial exploiting the potential of protons compared with photons to escalate radiation dose to 70 Gy while applying strict dose volume constraints to adjacent normal tissues (NCT01993810). In summary, while numerous advances in thoracic RT for Stage III NSCLC were introduced over the last 20 years, local tumor control and overall survival need refinement and no single RT technology/RT dose and fractionation have been identified as the most optimal approach. (1) Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. LancetOncol. 2015 Feb;16(2):187-99. PMID: 25601342 (2) Chen AB, Neville BA, Sher DJ, Chen K, Schrag D. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol. 2011 Jun 10;29(17):2305-11. PMID: 21537034 (3) Chen AB, MD, Ling L, Cronin A, Schrag D. Comparative Effectiveness of Intensity-Modulated Versus 3D Conformal Radiation Therapy Among Medicare Patients with Stage III Lung Cancer. J Thorac Oncol. 2014;9:1788–1795 (4) Nguyen QN, Ly NB, Komaki R, Levy LB, Gomez DR, Chang JY, Allen PK, Mehran RJ, Lu C, Gillin M, Liao Z, Cox JD. Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II–III inoperable non-small cell lung cancer. Radiother and Oncology, e-published May 2015